Psychiatric Aspects of HIV Invection and AIDS

8/18/2019 Psychiatric Aspects of HIV Invection and AIDS

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PSYCHIATRIC ASPECTS OF HIV INVECTION AND AIDS

John Querques, MD, and OliverFreudenreich, MD

KEY POINTS

*highly active antirertroviral therapi (HAART) has transformed infection with the

human immunodeficienci virus (HIV) from a terminal illness to a chronic, treatale

condittion!

*psyhiarric and sustance use disorders are fre"uent concomitans of HIV infection

and complicate its diagnosis and treatment!

*eva#uation of effective, ehavioral, and cognitive symtoms must e road and

indude primary psychiatric disordersand secondary conditions related to HIV

infection, apportunitic infections, and neoplasms!

*ecause oth psyhotropic and antiretrofiral agents are metaoli$ed y the

cytochrome %&' en$yme system, pharmaco#inetic interactions etween these two

classes of medication must e considered when treating psychiatric disorders in

HIV&invected patients!

*successful psychiatric treatment can e life saving if poor adherence to HAART itdue untreated psychiatric illness!

OVERVIEW

once adread illness that portended certain death after years or even +ust months of

ineorale decline, infection with HIV has ecome a chronic, treatale illness! the

advent of HAART -.. mar#ed a critical turning points in the pandemic various

cominations of potent medication, each targeting a different step in the virus/s

hi+ac#ing of its human host reduced the incidence of the ec"uired immunodeficiency

syndrome (AI0) and improved life epectancy for many patients with HIV

infection! 1ell into the fourth decade of the epidemic now nearly 2 medications and

increasingly in developing areas!

The successes of the past 2 years notwithstanding, diagnosis with HIV

infection still foreshadows an arduous course of fre"uent eaminations, serial

monitoring of cell count and viral load, and difficult treatments with potentiall


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disaling and disfiguring adferse effects (e!g, neuropathy, lipodistrophy)! 3ffective

treatment is not otainale in all parts of the world, and, even in countries where

medicarion are availale, not all patients have access to them! At each step of whathas een termed the HV care cascade, significant attrition curtails the numer of

patients who receive the evaluation and care te"uired to achieve the most critical

outcome&full viral suppression! 4or eample, on the 5 in 6., 7-!.8 of HIV

infected people #new their status, 9!78 received care 29!:8 stayed in treatment,

26!:8 received HAART, and only 6!28 achieved viral suppression! ;lac#s and

Hispanics


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0uring the first wee# after infection, the population of =0' tlymphocytes (i!e,

the =0' count) decreases as the amount of virus in the lood (i!e, the viral load)

increases (figure :&2)! 4ollowing a wee# and short&lived reound, the =0' countsteadily declines! At the same time, the viral load oscillates around a @set&point until

ultimately viral replication intensifres and peripheral viremia surges! Administration

of HAART, when effectife, halts this process! Bpportunistic infections (Bls),

neoplasms and neuropsychiatric conditions occur with increasing fre"uency as the

immune deficiency worsens, prophylais for certain Bls (e!g, pneumocystis jirovecii

( formerly pneumochystis carinii) pneumonia and tooplasmosis) is instated during

the course of infection according to the =0' count!

CLASSIFICATION AND DIAGNOSIS

According to the =enters for 0isease =ontrol and prevention (=0=) , AI0 is

defined y a =0' count elow 6 cells (or less than -'8 of total lymphocites) or the

preence of an AI0 defining condition (box :&6)!

Infection with HIV is usually diagnosed in two steps! The initial test is an

en$yme lin#ed immunosorent assay (3CIA)! A positive result on this test is then

confirmed y a western lot test! ;ecause one&fifth of HIV infected people in the 5

are unaware of their serostatus, the =0= and the united states!

BOX 57-1 why are the principles of HIV psychiatry importand

*many patients with HIV infection have psychiatric prolems, oth antecedent and

conseuent to contracting the virus!

*many patients with psychiatric prolems have HIV infection, in part related to poor

+udgment!

*patients wiith HIV infectuion develop medical prolems that can manifest as psychiatric illness!

*patients with HIV infection ta#e medications with effective, ehafioral, and

cognitive effects and that interact with psychiatric agents!


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HIV-1 VIRION!

Figur 57-1! human immunodeficiency virus %R, protease, R?A, rionucieic acidD

RT, reverse transcriptase!

"igur 57-#! Cife cycle of HIV!

%reventive services tas# force (5%T4) recommend that HIV testing e done a part

of routine clinical care for all patients, regardless of ris# factors!

GENERAL APPROACH TO PSYCHIATRIC CARE

The approach to the psychiatric care of the patient with HIV infection focuses

accurate diagnosisD an appreciation of the


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Figur 57$! history of HIV infection with HAART!

BOX 57-# AI0 defining conditios

• =andidiasis

• =ervical cancer, invasive

• =occidioidomycosis

• Eryptococcosis

• Eryptospondosis

• =ytomegalovirus disease of retinitis

• Harpes imple virus infection• Hitoplasmosis

• HIV related encephalopathy

• HIV related wasting syndrome

• Isosponasis

• Faposis/s sarcoma

• Cymphoma

• >ycoacterial infection

• neumocystisjirovecli pneumonia

• %neumonia, recurre2nt

• %rogressife multifocal leu#oencephalopathy

• !atmonelia septicemia, recurrent

• Tooplasmosis, cereral!


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differences In response to, and toleraility of, psychotropic medications, and the

prognostic importance of optimal adherence to effective antiretroviral treatment,

which psychuiatric illness often compromises!

%sychiatric symptoms In a patient with HIV invection may e primary or

aecondary (:&2) the =0' count provides useful initial guidance in ma#ing this

dioferrential diagnosis! A =0' count greater than cell digests a primary

psychiatric cause, whereas a =0' count less than 6 cell and a "ortiori less that

call suggests the psycharic prolem is secondary to the effects of immune

compromise! 4or eample a patient who has +ust een told that he is HIV positive ut

whose =0' cuont is still normal and whose viraload is low may ecome depressed as

part of an ad+ustment disorder (a primary psychiatric prolem)! However, - years

later, when he again has depressed mood and his =0' count is - call, he may veryli#ely have an Bl or a neoplasm effecting his =? and causing depression (a

secondary psychiatric pronlem)!

BOX 57-$ 0ifferential diagnosis of psychiatri symptoms in the HIV infected patient!

0elirium

ustance intoication or withdrawal%rimatry HIV syndromes

eroconversion lines Acute HIV meningoencephalitis

HIV associated neuroognitive disorder

Bpportunistic infections

4ungi

• Apergillus fumigates

• =andida alicans

• =occodioides immitis

• =ryptoccous nooformans

• Histoplasma capsulatum

• >ucormycosis%roto$oa< parasites

• Ameas

• Tooplasma gondil

Viruses

• Adenovirus type 6


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• =ytomegalovirus (=>V)

• G= virus

• Variceila&$otrer virus;acteria

• Eram negative organism

• Cisteria monocytogenes

• >ycoacterium avium intracellulare

• >ycoacterium tuerculosis

• ?ocardia asteroids

• Treponema pallidum

?eoplasms

%rimaru =? lymphoma

?on&hodg#ins lymphoma>etastatic #aposi/s sarcoma (rare)

>edication side effects

3ndrocinopathiesand nutrient deficiencies

Addison/s disease (=>V)

Hypothyroldsm

Vitamins A- ;9- ;-6 and 3 deficiencies

?on&HIV related conditions

HIV human immunodeficiency virus!

0istinguishing etween primary and secondary causes has therapeutic implications

ecause of standard psychiatric treatment for secondary prolems may e inferior to

those achieved if the prolem were primary! As in a patient with traumatic rain

in+ury, stro#e, dementia, or advanced age, then rain of a patient with HIV Infection

can e considered to e more sensitive to psychotropics and to have less reserve

caaclty! Thus a standard dose of a psychoropic medication may have a more (or less)

profound effect in an HIV infected patient or may cause adverse effects that usually

occur only at higher dosages!Bptimum treatmet of HIV infection and releted conditions is essential for effectice

psychiatric care! =lose collaoration etween the psychiatrist and the physician

providing the HIV care is crucial!


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BOX 57-% Adverse effects of sustance use in the contet of HIV infection

• Impaired +udgment

• 0insihiition• Ris#y seual practices

• Viral transmission

• Interactions with psychotropic medications

• %oor adherence to antiretroviral therapy

• %ossile immune suppressions

PSYCHIATRIC DISORDERS

Su&'()* +, Di,r.r,

utance use disorders are well represented among HIV infected patients! The month

prevalence of drug dependence in the HIV costand services urili$ation study

(H=5) a study of a nationally reprensetative sample of nearly 2 HIV infected

adults in the 5 was -6,8 sustance use disorders affect the transmissions, course

and sustance of HIV infections in numerous ways (o :&')!

o called @clu drugs methylenedioymethaphetamine (>>0>A,

@ecstasy), gamma hydroylutyrate (EH;, li"uid ecstasy), and #etamine (special

F) and other related compounds have ecome increasingly popular drugs of ause,

in part ecause of their effects on social disinhiition and seual enhancement! As a

result they can pave the way to HIV transmissions! ;y virtue o pharmaco#ineticinteractions with the cytochrome %&' system, the co administration of @clu drugs

with antiretroviral medications can have harmful conse"uences! Adverse effects of

>0>A and EH;,thought to e due to interactions with protease inhiitors, have

een reported! %rotease inhiitors, especially ritonavir, may inhiit the metaolism of

amphetamines and #etamine !

>any stresors during the course of HIV infection threaten oth the

estalishment and the maintenance of soriety In patients with sustance use

disorders (o :&)!

Interactions etween methadone and various antiretroviral agent are presented

I o :&9! 1hile these interactions may produce measurale changes In methadone pasma levels, such alterations do not consistenly result In clinical manifestations!

1ithdrawal phenomena have een oserved with efaviren$, nevirapine, and

nelfinavir!

Cess In #nown aout uprenophine, whice, li#e methadone, is metaoli$ed y

cytochorome %&' 2A'! The co&administration of uprenorphine and efafiren$ to -


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volunteers sis not precipitate oploid withdrawal, despite decreased uprenorphine

eposure, efavirens plasma levels remained therapeutic! The comination of ritonavir

and ata$anavir caused symptoms consistent with opioid ecess when given to three patients also ta#ing uprenorphine, pharmaco#inetic, measures of huprenorphine and

the two protease Inhiitors were not reported! ;uprenorphine/s partial agonism at

opioid receptors limits its utility in patients who re"uire narcotic analgesics, as many

HIV infected patients do!

The oral solution of amprenavir contains propylene glycol, which is

metaoli$ed y aldehyde dehydrogenase! 0isulfiram iniits this en$hym and can

thus lead to propylene glycol toicityhy, therefore, the comination of disulfiram and

amprenafir oral solution is contraindicated!

BOX 57-5 treesors 0uring HIV Infection

0iagnosis and treatment

• Testing seropositive

• erial determinations of =0' count and viral load

• Initiation of highly active antiretroviral therapy

• Initiation of prophylais for opportunistic infections

• 4irst hospitali$ation

•

Transfer to hospice care 3perience of symptoms

• 1asting

• 0iarrheal illness

• Treatment&resistand pain and insomnia

• Vision impairing disease

• =ognitive and motor dysfunction

• ide effects of medications

%sychosocial conse"uences

• 0isclosure of HIV serostatus

• 0isclosure of seualorientation

• Coss of employment and health insurance

• Application for welfare and disaility insurance

• 4inancial and social impoverishment!


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BOX 57-/ interactions etween methadone and antiretroviral agents

Antiretrovirals that decrease methadone concentrations• Amprenafir

• 3faviren$

• 4osamprenafir

• Copinavir

• ?elfinavir

• ?evirapine

• Ritonavir

>ethadone decreases the concentration of

• 0idanosine

• tavudine

>ethadone increases the concentration of

• idovudine

D0r,,i A). A)2i'3 Di,r.r,

>ood and eniety disorders are two of the most fre"uent ma+or psychiatric

cincomirtants of HIV infection! In the H=5, 298 screened positive for ma+or

depression, 69,8 for dysthymia, -!78 for generali$ed eniety disorder, and -!8

for panic attac#! 1hile individual studies have failed to document a greater ris# for

depressive disorders in HIV positive patients compared to HIV negative controls, ameta&analysis found the fre"uency of ma+or depressive disordes to e nearly twice as

high in the HIV positive group! This finding may suggest that the various

conse"uences of HIV infection (e!g, effects of the virus within the =?, immune

dysfunction, and systemic viral urden) eert a depresogenic effect!

BOX 57-7 differential diagnosis of depression and aniety I the HIV infected patient!

• ?ormal epressed or anious mood

• Erief

• %rimary depressive disorder

• %rimary anety disorder

• HIV associated neurocognitive disorder

• Hypoactive delirium

• econdary causes


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The differential diagnosis of depression and aniety is road (o :&:)! The patient/s

complaint of @depression or @aniety should e ta#en solely as a decription of his

su+ective! The patient may simply have a depressed mood or fell anious, isolatedfrom other symptoms and signs of psychiatric illness! uch a state, for eample,

would not e unusual in a patient who is starting an antiretroviral regimen! 0ysphoria

or apprehension I this situation may e more consistent with grief over loss of health!

>oreover, ecause of their drug use or seual orientation, many HIV patients have

friends who also are HIV positive! 1hen these friends die of the discase,

ereavement can overwhelm the surviving memers of their social circles! >any

patients, particularly women, will have eperienced psychological trauma due to

childhood ause and parner violence and may have post&traumatic stress disorder,

which can e easily missed without specific in"uiry!

At later stages of illnesss, Bls and neoplasms effecting the =?, other

complicatins of advanced disease, cognitive disorders, and dverse effects of HAART

can cause secondary depressive disorders delirium and HIV associated

neurocognitive disorders (HA?0), including HIV associated dementia (HA0), are

characteri$ed y apathy and psychomotor, slowing that can easily e mista#en for a

depressive disorder!

Treatment of depression and aniety includes the usual modalities

psychopharmachologi , psychotherapy, and electroconvusive therapy (3=T)!

=hoice of psychotropic medication is not usually, limited y the presence of

HIV infection per se# however, owing to the sensitivity of the rain in HIV infected patients, especially at later stages, initiation of treatment with half the usual starting

dose and titration at half the usual speed is recommendedD most patients will

ulyimately tolerate (and need) standard doses! Tricylic antidepressants (T=As) may

have an advantage In this regard ecaus etheir serum levels can e measured to gauge

any pharmaco#inetic effects of pshchomotor slowing is prominent due to depression,

dementia,or oth (or in uclear cases) psychostimulans, upropion, or desipramine can

e particularly effective! ;upropion is metaoli$ed y cytochrome %&' isoform

6;9, which is inhiited y ritonavir, nelfinavir, and efaviren$ and induced y

nevirapine! The tria$oloem$dia$epines alpra$olam, mida$olam, and tria$olam are

metaoli$ed y cytocrome %&' 2A', an isoform inhiited y protease inhiitors(%Cs)m which can thus enhance the effects of these aniolytics! 5se of those

en$odia$epines n patints on HAARTis relatively contraindicatedD other

en$odia$epines should cosdere!

3=T can e lifesaving when a more rapid resonse is re"uired and when

catatonia is present!


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P,3*4'i* Di,r.r,

HIV Associated %sychosis

%sychosis can occur at any time during the course of HIV diease and complicate its

treatment! The differential diagnosis for new onset %sychosis a patient wuth HIV

invection is very road, it includes delirium, HA0, Bls, other illnesses (e!g,

neurosyphilis), side ffects of medications, and drug use special wight should e given

to past stimulant and sedative use disorders, ecause these increase the ris# for the

later development of %sychosis! in cases of secondary %sychosis, cognitive

impairment is typically seen! In the 5, new onset %sychosis without other signs of

AI0 is only rarely the presenting sign of HIV infection! In one study of 6'9 patients

with new onset %sychosis reffered to a military hospital,none was positive for HIV! In

some HIV&infected patients,psychosis wiil mar# the onset of schi$ophrenia and wiil

e unrelated to the infection!

The treatment of phychosis in the setting of HIV infection involves treating

oth any underlyng disorder and psychosis symptomatically whit antipsychotics!

econd&generation antipshchotics are often preferred over first Jgeneration agents

ecause of the letter/s higher ris# for inducing etrapyramidal simtems (4%) in

patients with HIV disease! Hewever, the similar metaolic side&effect profiles of

second&generation antipshchotics and HAART (i!e, glucose intolerance and

dslypidemias) compliate the ris#&enefit e"uation with regard to long&termcardiovascular mortality! 1hile clo$apine can e used in patients with HIV

disease ,the additive one marrow toicities from clo$apine and many medications

used in HIV care should e seen as a rela"tif contraindica"tion !

Antipshchotics do not significantly inhiit or induce2 %&' en$imes and

can savely e added to HAART regimens without fear of causing HAART failure or

toicity HAART regimens may accelerarte the metaolism o antipsychotics (leading

to antipsychotic failure ) or inhiit the metaolism of antipsychotic (leading to a

higher ris# of dose&related antipsychot ic side effects), dependin on the comination

used! %otentially cariotoic antipshchotics&particulary pimo$ide ,droperidol and

thiorida$ine should not e copmined with HAART !To avoid further rain compromise, anticholinergic medications to manage

antipsychotic induced 3% should not e used over the long term! Instead,

antipsychotics that do not re"uire the concomitant use of anticholinergics

arepreferred!


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AIDS MANIA

A clinical entity of mania with cognitive impairment ut without a personal or familyhistory of iporal disorder has een termed $%D! mania, a form of secondaty mania

that tenss to occur in late stage HIV disease! In one study from 5ganda, a country

with high HIV prevalence, 9- ('28) of -'- hospital admissions oracute mania were

for HIV related secondary mania! =linically, the full manic syndrome is presents,

often more severe than prymari mania and accompanied y significant phychosis!

The mood is typically arritale and paranoid and rarely euphoric! %rofound sleep

disturance causes patients to e confused and up all night delirium must e eclude!

Treatment includes initiating or optimi$ing HAART, ut it is otherwise identical to

standard mana+ement of ipolar disorder! In more severely lll HIV infected patients,

antipsychotics are preferred ove anti manic mood staili$ers ecause of relatively

poor chinical toleraility for lithium and cara$epine ecause of increased ris# for

liver toicity for valproate! Valproate can enhance the ris# for one marrow toicity

when comined with $idovudine ecause of increased $idovudine lood levels!

COGNITIVE DISORDERS

Diriu6

0elirium must e considered in a patient with HIV infection who has any alteraton in

mental status, including new onset phychosis! 0elirium is often m#ista#en for depression or aniety, which can overshadow thwe cognitive impairments cause of

delirium in this populations are myriad and some are listed in o :&2 often, several

causative factors are present simultaneously, evaluation of delirium in HIV infected

patients must include rare causer! In immunocompromised patients, delirium might e

the sole sign of an infection! 0elirium is discussed at greater length in chapter -7!

HIV-A,,*i('. Nur*g)i'i Di,r.r

%erhaps ecause HIV invades the rain shortly after infection, cognitive complaints

and prolems at some point during the life course are common in HIV infected

patients! ;efore HAART the ma+ority of patients developed cognitive prolems,including a late stage sucortical dementia, currently termed HA0 (previously refrred

to as AI0 dementia or AI0 dementia comple), part of a wider spectrum of

neurocognitive impairments collectively called HIV associated neurocognitive

disorder (HA?0)! 1hile the incidence iof HA0 has declined since the inrtrodution of

HAART, that even HAART treated patients can manifest the less severe forms of


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HA?0 asymptomaic nerocognitive impairtment and mild nerocognitive disorder is

incteasingly recogni$ed! It is li#ely that phenotypic differences eist among HA0

patients some patients have irreversile deficits (accrued in theasence of HAARTduring times of prolonged and high viremia and poor immune function), whereas

newly diagnosed patients might recover sustantially if treated with HAART, even if

they have HA0! ome cohorts might have other pathophysological processes adding

insult to in+ury! 4or eample the hepatitis = virus (H=V) has een shown to e

neurotropic and signivicannt past of active drug use can further impair rain function!

As a sucortical dementia , HA0 is characteri$ed y disturances of moodm

memory, and motor function (o :&7)!

BOX 57- clinical features of cognitive disorders in the HIV infected patient!

>ood

• Apathy

• 0epression

• Anlety

• Hypomania

• 0isinhiition

• %oor +udgment

• %ersonality change

>emory• Impaired attention

• Impaired concentration

• Impaired memory

>otor function

• >ental asnd psychomotor slowing

• Incoordinator

• Eait prolems!

Impairments in attention, new learning, processing speed and eecutive function caue

significant disaility! 0epression and aniety are often present and can eclipse the

cognitive prolems! >otor and cognitive slowness can e pronounced ehavioral

prolems ranging from apathy to hyomania and disinhiition can greatly complicate

management, particularly if +udgment is impaired!

Any HIV infected patient should e carefully assessed for cognitive prolems,

particularly if periods of high viremia and low =0' counts occurred in the past! It is


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useful to screen for cognitive prolems with the HIV dementia scale (H0) or its

modified form (tale :&-), supplemented y other edside tests (e!g, luria hand

maneuvers and veral forms of the trail ma#ing tests A and ;)! the folstein minimental state eamination (>>3) is not sensitive for sutortical dementias

particularly if mild! ;ecause it does not include timed tas#s, it is relatively poor at

detecting the psychomotor slowing that is the hallmar# of HA0!

=omprehensive neuropsycholopghical testing should e ordered to clarivy the

diagnosis, for longitudinal assessments, and to delineate further the nature and

severity of detected or suspected deficits! However there can e a discrepancy

etween test csores and functional capaility, and a patient/s complaint aout

cognitive difficulties should not e dismissed! In addition depression should e

considered and a time limited antedpressant trial e offered when the diagnosis is

unclear!

Reconition of cognitive impairment is important since patiens with eecutive

dysfunction and poor memory, left to their own devices, may e unale to participate

in their HIV treatment anf to adhere optimally to HAART, thus setting up a vicious

cycle of eacerated rain dysfunction into account, and sufficient support must e

provided to compensate for these deficits!

The optimal HAART reiment dor patints with =? disease (or to prevent

=? disease) remains to e estalished! 1hile it is unclear if regiments with

antiretrovirals that penetrate the =? (i!e, $idovudine, stavudine, aacavir, and

nevirapine) are superior to other regimens! There is consensus that optimal peripheralviral suppression is necessary! Treatments for the dementia it self are eperimental

(e!g, anticholinrgics) should e mini$ed or avoided and sustance use disorders

treated! Any patient who is suspecte to have a primary depressive or aniety disorder

must atsoe assessed for HA0! Bften, the issue cannot e resolved on dlinical

grounds, and an antidepressiant trial is anitiated in con+unction with HAART

optimi$ation! A dementing illness coupled with impulsivity increases suicide ris#!

NE+ROLOGICAL DISORDERS

everal central neurological conditions are AI0 defining conditions (;o :&6)

cytomegalovirus (=>V) encephalitis, cryptococcal meningitis, HA0, primary =?


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lymphoma, progressive multivocal leu#oencepholapathv (%>I, figure 2:&'), and

cereral toopiasmosis ( figure :&)! ;oes :&. and :&- provide a more

etensive list of neurological conditions associated with HIV infection! %atients withthese disorder are usually acutely ill, and they are treated y neurologists and

internists in hospital setting! %sychiatrists get involved when ehavioral

manifestations (e!g, depression or psychosis) are prominent and when, following the

acute treatment phase, patients have to ad+usts to a new diagnosis (which might

include AI0) and new disailities (e!g, loss of rain function after treatment of =?

lymphoma or virus impairment from =>4)!

Bne peripheral neurological complication distal sensory polyneuropathy

(0%) has emergt as a significant clinical prolem! It is the most common

neurological complication of HIV disease affecting approimately oe third of

allpatients! The etiologi of 0% is often a miture of macrophage driven never

damage and mitochondrial dysfunction caused y nerve toic nucleoside reverse

transcriptase inhiitors (?RTIs) ( the dideoynucleoside or @drugs dll, d'T, and

dd=) resulting in a aonal neuropathy! >any patients ear the urden of additional

toins (e!g, alcoholism, Bl prophylais, or pas treatment with vincristine for HIV

related cancers)! A lower =0' count is one recogni$ed ris# factor, others include

older age, lower hemogloin,and higher viral set point! Thus 0% encomplases two

phenotypically identical neuropaties HIV associared 0% and antiretroviral toic

neuropathy (AT?)!

As the most common neurological condition, 0% is importand for psychiatricfor two reasons (1) many long term patients suffer from it, resulting in a chronic pain

syndrome that can e ecruciating, resulting in disaility, depressive overly, and

recuted "uality of life, and (6) =?&active medications ae often re"uired to tread the

pain, adding iatrogenic moridity (e!g, fatigue)!


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Figur 57-%! progressive multivocal leu#oencephalopathy! (courtesy o" Dr#

$nderson)!

BOX 57-8 neurological complications of HIV infection

HIV associated neurocognitive disorder (HA?0)

>yelopathy (spinal cord disease)• Vacuolar

• %ure sensor

4ocal central nervous system (=?) lasions

• Tooplasmosis

• %rimary =? lymphoha

• %rogressive multyvocal leu#oencephalopathy

>eningitis

• Aeptic

•

=ryptoccoccosis• Tuerculosis

?eurosyphitis

Faposi/s sarcoma

=hagas reactivation

3ncephalitis


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• =ytomegalovirus (=>V)

• Herpe siple virus

?erophaties (see also :&-)

• HIV associated distal sensory polyneuropathy

• Antiretroviral toic neuropathy (due to the @d drugs ddl, dd=, d'T)

• Inflammatory polyneuropathies

• =>V polyradiculopathy

• >ononeuntis multiple

>yopathy

0% diagnosis rather pure sensory neuropathy with symptoms typical of

sensory neuropathies (i!e, tingling, pain, and urning on the feet)! In addition, an#le

reflees are often asent!

The diagnosis can e suspected on clinical grounds in the right settin and with

typical symptoms! ?erve conduction studies demonstrate an aonal neuropathy! In

unclear situations, partyulary when severe symotoms are not supported y signs, an

outpatient punh s#in iopsy can clarify the situation!in atients with 0%, the intra&

epidermal nerve fierdensity is reduced!

Treatment involves remofal of toic agentsD if the offending agents can e

discontinued, the neuropathy might resolve, since many HAART medications do not

cause neuropathy, regimens that do not contain high&ris# drugs (i!e, the @drugs) can

usully e found treatment of confounding conditions (e!g, alcoholism, diaetes) must e optimi$ed! In many cases, symptomasic treatment will e necessary! Treatment

include pain madications, anti&epileptic drugs, and T=s! In one well&controlled trial,

lamotrigine was effective! =arama$epine is difficult to use in this population

ecause of a higher rate of raches and leucopenia!

B2 57-19 Important causes of peripheral neuropathy in the HIV infected patient

HIV associated distal sensory polyneuropathy

Antiretroviral toic neurpathy (due to the @d drugs)

• dd= ($alticaine)

• ddI (didanosine)

• d'T (stadine)

0iaetes mellitus

Alcoholism

0iffuse infiltrative lymphocytosis syndrome


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Antiiotics

• 0apsone (used to treed pneumocystis +irovecli pneumonia and looplasmosis)

• Isonia$id (used to treat ameic tuerculosis)• >etronida$ole (used to treat ameic dysentery)

=ancer drugs

• %aclitael

• Thalidomite (used to treat aphthous ulcers and wasting)

• Vincristine (used to tread Faposi/s sarcoma)

TREATMENT

&he 'ey therapeutic modalities for HIV infected patients are psychopharmacology and

psychotherapy, often comined with providing social support and crisis intervention!

In general, patients with HIV infection particulary those at advanced stages of

illness have less lean ody mass, metali$e drugs more slowly, and are enitive to drug

side effects! ;ecause of lood rain arrier compromise, thw HIV infected rain may

@see higher levels of drug! Therefore, when sterting a psychotropic, start at half the

usual starting dose, tifrate half as fast as usual, and aim for low therapeutic levels,

these clinical rules of thum sould not e ta#en as ecuses for prescriing

sutherapeutic doses over prolonged periods of time, ecause most patiens wll

tolerate and need standart regiments!

everal classes of antiretroviral agents are currently availale to comat HIVinfection (tale :&6), and some have neuropsychiatric side effects! The ??RTI

efaviren$ carie$ the highest liaility for a road range of neuropsychiatric symptoms

(e!g, vivid dreams diiness, insomnia, depressive symptoms), affecting up to half of

patients! However, these side effects (mostly mild in nature and possily related to

plasma levels) are usually limited to the period of initiation of efaviren$! High dose

AT has een lin#ed to mania!

%otential interaction etween antiretroviral and psychotropic medications are

numerous, the 5niversity of Civerpool maintains a comprehensive online dataase of

these and other interactions at www!hiv&druginteractions!org, to which the interested

reader is referred for the latest information on this topic!

All of the ??RTIs and %Cs are metali$ed y the cytochrome %&' system

especially the 2A' isoform and many also induce or inhiit it (as well as other, non %&

' en$yme system)!

BOX 57-11 features of the @marathon model in psychotherapy

http://www.hiv-druginteractions.org/http://www.hiv-druginteractions.org/


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Training

• How have you coped with adversity in the past• %ersonal team

• 1ho comprises your personal support systemK

%it stops

• =an you ta#e a rea# from eing sic# y scheduling a wee# without doctors

appointmentsK

=orporate support

• 0o you have a primary care physician, HIV specialis, psychiatric, hospital,

health insurance, and employerK

Ritonavir is the most potent 2A' inhiitor if given at full dose (low& dose roitonavir is

often added to other %Is to @oost their levels) sa"uinavir the least some

antiretroviral agents (e!g, efaviren$) have comple interactions with the %&'

system, oth inhiiting and inducing it, thus complicating prediction of psychotropic

drug levels, especially with multiple drug regimens! In all cases, a high inde of

suspicion and close clinical follow&up are the est safeguards aganst drug

interactions! The most dangerous drug interactions are those that loc# the

metaolism of psychotropic with dose related toicity (e!g, pimo$ide, clo$apine,

tra$oloen$odia$epines T=As)! The ?RTIs and the fusion inhiitor enfuvirtide have

no %&' mediated drug iteractions with psychotropics! The entry inhiitor maravirocand the integrase inhiitor raltegravir have limited potential for interactions with

psychotropic! Acomination pill,striild (rand name), contains coocisrtat! A potent

2A inhiitor, that could potentially increase plasma levels of co&administered

psychotropics!

%sychotherapy with the HIV infected patient is more often supportive and

crisis&centered than eploratory and insightoriented! 4re"uently, one or more of the

stressors listed in o :& rigs the patient to therapy! The four #ey "uestions of the

@marathon model (;o :&--) identify the strengins the patient rings to ear on the

stressful situation and the wea#&nesses that will render its resolution difficult!

Through education, guidance, and advice, psychosociall assets are enhanced and

deficits remedied!

SPECIAL CLINICAL PROBLEMS


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A.4r)*

A high degree of adherence to HAART is necessary to minimi$e the ris# of medication failure and the development of rsistand HIV strains! 4or non&oosted %I&

ased HAART regimens, adherence approaching -8 is re"uired to supprss viral

replication, although adherence re"uirements for other regimens (e!g, those

containing the more potent ??RTIs) might e more @forgiving! >aintaining

adherence over an entire lifetime often proves challenging, even for the most

industrious patient!

%sychiatricsts can coitriute their part to optimi$ing adherence to HAART y

identifying and treating those psychiatric factors that can lead to poor adherence (;o

:&-6)! %sychiatrists should rountinely assess HAART adherence and educate

patients aou the importance of optimally controlled HIV disease for their mental

health! In many instances of poor adherence (e!g, if there is cognitive impairtent),

merely focusing on simpler HAART (or psychotropic) regimens is insufficient and

more active approaches are re"uired including enlisting the help of other people to

ensure proper ta#ing of medicationas (e!g, providing directly oserved therapy

(0BT)! Treating depression with fluoetine in homeless patients using 0BT hasd

een shown to e an effective intervention In achieving control of HIV!

BOX 57-1#! 4actors Affecting Adherence To Highly Active Antirertroviral Therapy

• 0epression

• $ctive sustance use

• =ognitive impairment

• %sychosis

• %ersonality factor that load to chaotic lives with no routines

• >edication fatigue

• 0emorali$ation

• Age L2 years

• ?on&discriosed status

• Health illiteracy

BOX 57-1$! 0ifferential 0iagnosis Bf 4atigue In The HIV Infected %atent


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tress

leep deprivation

• Insomnia• %ain

0ysoric mental states

• Aniety

• 0epression

Besity

0econditioning

0rug and alcohol use

>edication induced sedation

•

Highly active antiretroviral therapy• %sychotropics

HIV


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BOX 57-1% evaluation of faigue in the HIV infected patient

History

>edication review

4ocused laoratory wor#&up

• =omplete lood cell count

• =hemistries

• Thyroid stimulating hormone

• 4olate

• Vitamin ;-6

• Testosterone(in males)

• %regnancy test

• 3rythrocyte sedimentation rate

ustance use screening

Rating scales

• Aniety

• 0epression

• leep "uality

%olysomnography (if indicated)

1or#&up for cardiac disease and adrenal insufficiency (if indicated)

BOX 57-15 Ris# 4actors 4or uicide In The HIV Infected %atient

• >ale gender

• 0epression

• ustance use

• =ognitiveimpairment

• ame gender seual orientation

• tressors associated with living with a comple disorder

• Recent diagnosis of HIV diasease

• Terminal sttege of illness

S+ICIDE

After HAART was introduced, the suicide rate in the HIV population decreased!

However, all element of suicidal urden (i!e, thoughts, delierate self&inury, and


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completed suicides) are elevated among HIV positive pstients! In many instances, a

diagnosis of HIV infection is simply one additional stressor in a life already

complicated y sustance use and sychiatric moridity (;o :&-)! If HIV infection per se confers any additional ris# eyond generally #nown suicide ris# factors,

particularly sustance use and depression, is un#nown! >ore specific associations

etween HIV infection and suicide might eist (e!g, HA0 with mood laility,

mpulsiity, and poor +udgment may increase the ris# for suicide)! 3ven when

depression and sustance ure are controlled for, an association etween

homoseuality and suicide persists!

Sriu, M)'( I),,

A small miorit of patients with schi$ophrenia and other serious mental illnesses

(>Is) are infected with HIV, with estimates ranging from 2!-8 to 78! This

population is often overloo#ed as eing at ris#, despite a high rate of lifetime

sustance use and other ris# factors, including trasing se for money! In one survey,

patients with schi$ophrenia were rather misinformed aout the transmission of HIV!

creening for HIV infection that into account cognitive

Cimitations have ecome important roles of providers who treat patients with >I!

Importantly, sustance use more than >I per se is the driving force ehind newlyec"uired HIV infection!

=omple treatment regimens are est avoided, and second gereration

antipsychotic are preferred over first generation agents to avoid 3% and the need for

anticholinergics! 0rug interactions etween antisychotics and HAART should e

anticipated, and antipsychotics drug levels should e measured to ensure ade"uate

concentrations and avoid psychotic relapse! ;ecause of the severity and chronicity of

their mental illness, many patens with >I are well connected to sychiartric and

medical services and life in supervised settings, so adding HIV treatment poses fewer

difficulties than usually feared! However, a group of so called @triply

diagnosedpatents HIV infection, >I, and sustance use poses particular challengesin treatment engagement and adherence! If a psychotic eaceration occurs in a

patient with >I and HIV disease, causes related to HIV, its complications, or its

treatment must e ruled out efore attriuting the eaceration to the psychiatric

illness!


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C-I)"*'i) Wi'4 Hi A). H0('i'i, C

Approimately -8 to 28 of patients with HIV diseae are also infected with H=V!This @co infected cohort is rather different from HIV @mono&infected patients with

regard to ris# factors and psychiatric illnesses! >ost patients have ec"uired H=V

from in+ection drug use, the main mode of transmission for H=VD the group s

marginali$ed with high rates of homelessnessD and there might e a higher rate of

antisocial tendencies or personality disorder! Accordingly, psychiatric treatment

focuses on cessation of sustance use and prevention of relapse!

Alcoholism is often present and can lead to additional live damage! However,

recent outrea#s of acute hepatitis = infections have confermed a role for seual

transmissions of H=V as well, particularly among >>! As treatment of, and

survival with, HIV disease have improved, liver failure from hepatitis = infection has

ecome a ma+or cocern in this cohort, and patient are increasingly treated as the

newly availale directly acting antivirals telaprevir and oceprevir when comined

with interferon, have improved the outloo#for clearing hepatitis = infection!

?europsychiatric side effects of interveron are common and can lead to depression,

suicide, and relapse to sustace use!

Cig(r'' S6:i)g

As mortality due to HIV causes has steadily decreased, intervention has focused onother causes of premature death, including cardiovascular disease! A ma+or

contriutor to cardiac ris# as well a cancer and pneumonia in HIV infected patients Is

smo#ing! An estimated '8 to 78 of person with HIV are current smo#ers! 1ith

epertise in addictions, psychiatrists can e critically involved motivational inter&

viewing and assisting motivated smo#er to "uit smo#ing, using standard approaches

including nicotine replacement therapy! Varenicline appears to e as afficacious and

tolerale in HIV infected patients as In the general population!

BOX 57-1/ useful internet resources

A3EI (AI0 3ducation gloal information ystem)

• www!aegis!org

http://www.aegis.org/http://www.aegis.org/


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AI0info (5!! 0epartment of health and human services)

• www!aidsinfo!nih!gov

American psychiatric association AI0 resource center

• www!psych!org


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infection and ris# for depressive disorders! $m sychiatry -7:6&:2,

6-!

-.! >achtinger 3C, 1ilson T=, Haere G3, et, al! psychological trauma and %T0

in HIV positive women a meta analys! $%D! 9ehav -96.-&6-, 6-6!

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69! =lifford 0;! Human immunodeficiency virus assoiated dementia! $rch

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6:! Antinoni A, Arendt E, ;ec#er GT, et al! 5pdated research nosology for HIV

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Psychiatric Aspects of HIV Invection and AIDS

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