herbal medicine in the management and treatment of hiv-aids - a review of clinical trials

7/21/2019 Herbal Medicine in the Management and Treatment of HIV-AIDS - A Review of Clinical Trials

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Australian Journal of Herbal Medicine 2014 26(3)Article Australian Journal of Herbal Medicine 2014 26(3)Article

© NHAA2014 1010 © NHAA2014

se,ua intercourse& *ood transfusions& !y$odermic

needes& $re'nancy& *reastfeedin' and *ody fuid

e,$osure to sensitive

use of traditiona medicine is es$eciaycommon in

deveo$in' countries (i"e" Africa& Asia and

atin/Sout! America)" In deveo$in' countries&

an estimated 0 to 506 of t!e $o$uation use

traditiona medicines %!ic! mainy serve t!eir $rimary !eat!care needs" n t!e ot!er !and& in

deveo$ed countries (i"e" Austraia& 7uro$e and

8ort! America) traditiona medicine is commony

used in $arae %it! ao$at!ic medicine (i"e" !i'!y

active antiretrovira t!era$y (HAA9#))"2 #!e

use of com$ementary and aternative medicines is

%ides$read in c!ronic conditions& incudin' HIV-

AIDS infection" 7ven t!ou'! !er*a medicine is

one of t!e most commony used traditiona

medicines& statistics on t!e utiisation of !er*a

medicine in t!e treatment and mana'ement of HIV

amon' t!e Austraian $o$uation are ar'ey

unavaia*e" Accordin' to a :S study& 26



of HIV-infected $eo$e use !er*a medicine as $art of

t!eir treatment"3 A 7uro$ean study s!o%ed t!at !er*a

medicines are used *y a$$ro,imatey 2;6 of HIV-

infected $eo$e"4

#!e $rimary reason for t!e use of traditiona

medicines in t!e treatment of HIV& es$eciay in

deveo$in' countries& is t!e !i'! cost and/or t!eunavaia*iity of HAA9#"; Her*a medicines are more

i+ey to *e used in HIV-AIDS treatment in %estern

countries as an adunct t!era$y to su$$ort t!e immune

system& reduce t!e side-effects of medication (for

e,am$e nausea and de$ression)& reduce vira

re$ication and im$rove 'enera %e*ein' (i"e" act as an

ada$to'en)" Her*a medicines may function in different

%ays in HIV infection and associated conditions" In

many cases t!e mec!anisms of action are not cear and

t!e %!oe !er*s or s$ecific $!ytoc!emicas require

furt!er researc!" < 7mer'in' evidence su''ests t!e

$ossi*iity of immune-moduatory and anti-vira

$ro$erties conferred *y various !er*a s$ecies and t!eir

e,tracts" #!ere are !o%ever concerns reated to unsafe

or erroneous $ractices as %e as t!e increasin'

frequency of caims of a cure %!en t!ere is insufficient

evidence to su$$ort suc! caims"; In addition& !er*s or

t!eir $!ytoc!emicas may dis$ay adverse effects in

conunction %it! anti-retrovira dru's and may *e

contraindicated for use %it! t!ese medications" A ist of

commony used !er*s in HIV-AIDS adunct t!era$y is

s!o%n in #a*e 1"

$ethodolog*

A revie% of cinica trias avaia*e on t!e use of !er*a medicine in t!e treatment of HIV-AIDS or in

conunction %it! conventiona anti-retrovira dru's %as

conducted usin' =u*>ed and ?oo'e Sc!oar data*ases"

#!e ourna artices %ere o*tained usin' res$ective

onine ourna data*ases" #!e seection criteria %ere

restricted $rimariy to cinica trias e,aminin' !er*a

medicine in HIV-AIDS treatment& and !uman !eat!

surveys of A> use from @ anuary 15B0 - 30t!

Se$tem*er 2013" In vitro studies %ere incuded if t!ey

su$$orted t!e e,$anations of o*servations made in t!e

cinica trias to ea*orate on t!e moecuar mec!anisms

and e,$ain t!e o*served efficacy of t!e $articuar !er*amedicine"

#!e searc! terms incuded t!e foo%in' strin' of

terms in com*inationC

HIV Her*& AIDS Her*& HIV Her*a&

AIDS Her*a& HIV AIDS Her*a& HIV

AIDS Her*"

=u*ications %ere seected if t!e term(s) a$$eared

in t!e $u*ication tite" Aso a num*er of $u*ications

%ere o*served in muti$e or a of t!e searc! terms and

t!eir res$ective com*inations" Du$icates %ere removed"

9esuts of t!ese searc! terms can *e seen in #a*e 2"

Her*a medicines revie%ed incuded estern !er*amedicine s$ecies& #!ai& !inese and aso African

s$ecies" At!ou'! t!ere %as some an'ua'e restriction

t!e revie% attem$ted to incude !er*a medicines from

$u*ication in an'ua'es ot!er t!an 7n'is! %!ere t!e

!er*a s$ecies is found to *e ceary identified" #%o of

t!e aut!ors read >andarin (Han c!aracter scri$t) and

%ere a*e to determine t!e 'enus and s$ecies of some of

t!e !er*a medicines used in !inese medicine

treatments" #!e revie% aso focused on t!e safety andefficacy of !er*a medicine" After researc! $u*ications

and revie%s %ere com$ied %it! res$ective searc! terms&

ony !uman cinica trias and e$idemioo'ica studies

%ere used for t!e revie% (=u*>ed data*ase)" it!

res$ect to ?oo'e Sc!oar& t!e searc! term(s) %ere

required to *e incuded in t!e tite of t!e artice" Artices

re$eated %it! different searc! terms& data*ases& as %e

as some studies %it! no maor reevance to HIV-AIDS

%ere deeted from t!e revie%" =u*ications %ere

accessed directy from t!e $u*is!er %e*sites" 9esuts

from studies %ere e,amined suc! as num*er of

o*servations& ty$e of researc! desi'n& and maor

outcomes of t!e study" A discussion of t!ese resuts and

concusions %as conducted& sometimes usin' in vitro

studies as references to inter$ret t!e resuts s!o%n in t!e

researc! artices"

,es#lts

As #a*e 2 de$icts& t!ere %as a !i'! num*er of

cinica trias re$eated for different searc! terms (426)

t!at %ere deeted" Eurt!er& t!ere %ere anot!er 15"<6 of

$u*ications %!ic! !ad no direct reevance to HIV-AIDS

(#a*e 2) and su*sequenty deeted from t!is revie%"

#!ere %ere 33 cinica studies and e$idemioo'ica

studies finay seected and ta*uated for t!e revie% %it!maor outcomes of t!e researc! isted (#a*e 3)"

Disc#ssion

,ole of herbal medicinein HIV-AIDS

treatment

ny a fe% cinica trias are avaia*e on t!e use

of !er*a medicine in HIV-AIDS" #!ey are often

administered due to t!eir o% cost %ide avaia*iity in

t!ird %ord and deveo$in' nations %!ere anti-retrovira

dru's are not easiy accessed" ne issue is t!e mis'uided

!eat!care $rovided *y uneducated and unquaified

!er*aists misuse of !er*a t!era$y in t!e treatment of

HIV-AIDS in t!e t!ird %ord and deveo$in' nations&B

at!ou'! t!is may re$resent traditiona use of t!e !er*a

medicines for infection and infammatory conditions"

In t!e deveo$ed %ord A> treatment a$$ears to

*e %idey used in conunction %it! HIV conventiona

treatment suc! as anti-retrovira dru's" Her*a medicines

are used in com*ination %it! anti-retrovira dru's to

reduce adverse effects of nausea and de$ression and

for immune su$$ort/moduation" In t!e #!ird ord

and deveo$in' nations& due mainy to t!e cost of anti-

retrovira dru's& !er*a medicines a$$ear to *e more

%idey used& es$eciay in mana'ement of associated

conditions suc! as immune su$$ression and o$$ortunistic



infections" A study in >e,ico reveaed t!at of 253 HIV

$atients& <3"46 used A> of %!ic! 25"<6 %ere !er*a

$roducts" #!e correation of t!e use of A> %as !i'!est

in o%er income earners due to t!e $rice of anti-

retrovira treatment"5 In #an.ania& due to cost

restrictions& HIV sufferers resorted to t!e use of an

array of < ; !er*a medicine s$ecies& mosty eaf e,tracts and consumed as decoctions for t!e treatment of

associated infections suc! as tu*ercuosis and ora

candidiasis"F In :'anda& !er*a medicine treatment !as

*een o*served as a *eneficia treatment o$tion for

!er$es .oster virus (i"e" reduced $ain severity) in HIV

$atients"11

S#rve* of herbal medicine #sed in

treatmentof HIV-AIDS in &hailand

A study from #!aiand indicated t!at 31 6 of t!e

$o$uation re$orted usin' !er*a medicine" it! re'ard

to 'overnment su$$ort for modem treatment& t!e

study s!o%ed t!at $eo$e ivin' %it! HIV tended to

see+ assistance from !eat! care services for o*tainin'

treatment" Ho%ever& femaes ivin' in u$-country

areas received ess modem treatment *ut found !er*a

remedies more accessi*e for treatment" 9es$ondents

from $rovincia to%ns %ere found to use !er*a remedies

more often t!an t!ose from Gan'+o+ or !i'!y ur*ani.ed

areas& and t!e most commony used !er*a remedy (*y

21 6 of res$ondents) %as *itter cucum*er

(Momordica charantia).12

val#ation of herbal medicines #sed

for treatingHIV-AIDS in So#th AfricaIn a descri$tive& $ros$ective& foo%-u$ study in

Sout! Africa& 33 HIV-$ositive vounteers (< men and 2

%omen *et%een 22 and 43 years of a'e) %ere evauated

re'ardin' t!e effectiveness of commony used

traditiona !er*a medicines in t!e mana'ement of HIV-

AIDS" #!e study evauated t!e treatment efficacy

ofusin' !er*a medicines *y a num*er of quaitative

$arameters" #!e study %as conducted over a $eriod of

one year" =artici$ants s!o%ed si'nificant !eat!

im$rovement B06 of t!e $atients dis$ayed a *etter

$!ysica a$$earance& ;6 !ad increased a$$etite& <06

!ad disa$$earance of s+in mar+s/ esions&1006 !ad disa$$earance of uro'enita esions& and B06

of $artici$ants !ad 'ained *ody %ei'!t& at!ou'! *ody

com$osition %as not s$ecified" #!ere %as a si'nificant

decrease in vira oads %it! a corres$ondin' si'nificant

increase *y 2"; fod in D4 #-ce counts" ver 06 of

$atients resumed %or+$ace duties" #!e study stron'y

su''ested t!e effectiveness of t!ese traditiona Sout!

African !er*a medicines as su$$ementary or aternative

medicine in HIV-AIDS treatment& and t!e im$rovement

in vira oad su''ested t!ey !ad an anti-vira action" #!e

aut!ors su''ested t!e anti-vira activity may *e due to

t!e $!ytoc!emica com$osition of aendua officinaisor A'astac!e ru'osa& 13 %!ic! are used traditionay for

t!eir anti-s$asmoytic and anti-*acteria actions"

$od#lation of the imm#ne s*stem with

astragal#s

Astra'aoside II& a +ey $!ytoc!emica $resent in

Astragalus spp. , at a concentration of 1 nmo/&!as

*een s!o%n to initiate #-ce activation in $rimary murine

ce cuture (in vitro study)" #!e s$ecific mec!anism is

t!rou'! t!e re'uation of D4 ces via ; $rotein tyrosine

$!os$!atase activity (re'uates $!os$!oryation state of

various si'nain' moecues)& and may *e t!e s$ecific

mec!anism *y %!ic! astra'aus moduates t!e immune

system durin' disease& 14 incudin' HIV-AIDS"Astra'aus

(Astragalus spp.) %as traditionay used as a tonic for

dia*etes and as an ada$to'en for !eain' in !inese

medicine"

Assessment of lmm#no.el in treatmentof

&/ among HIV-AIDS atients

#!e !er*a medicine (Immuno,e) %as administered

%it! anti-#G t!era$y (A##) amon' HIV-AIDS $atientssufferin' from tu*ercuosis" Eorty $atients %ere divided

into t%o arms of t!e studyC arm A %as treated %it! A##

and arm G %it! Immuno,e ; A##" Immuno,e com$rises

of 2< immunoo'ica moduatin' !er*a s$ecies" #!ese

incudeC aoe (Aloe arborescens), centaury (Erythraea

centaurium ) , $arsey root (Petroselinum crispum),

rose!i$ (Rosa laevigata), !i'!*us! cran*erry fruits

(Viburnum opulus) , !y$ericum (ypericum per!oratum),

!inese a'rimony (Agrimonia pilosa), sea *uc+t!om

*erries (ippophae rhamnoides), sa'e ("alvia

o!!icinalis), *irc! eaves (#etula s$")& mari'od fo%er

($alendula o!!icinalis) ,

$antain (Plantago ma%or) ,

Si*erian 'insen' (Eleutherococcus senticosus), common

%orm%ood (Artemisia absinthium), inden (&ilia

cordata), uni$er *erries ('uniperus communis), rose root

(Rhodiola rosea), 'round ivy ( lechoma hederacea),

ore'ano (riganum vulgare), nette eaf (*rtica dioica),

icorice (lycyrrhi+a s$")& conefo%er (Echinacea

purpurea), %id t!yme

( &hymusserpyllum), equisetum (Euisetum arvense),

%id stra%*erry (-ragaria vesca), c!a'a mus!room

(Inonotus obliuus) and 'reen tea (&hea sinensis). :t %as

o*served t!at addition of Immuno,e reduced

o$$ortunistic infections as %e as im$roved cinica

efficacy of A##"1<

?iven t!e %ide array of !er*a s$ecies it is uns$ecified

%!ic! $!ytoc!emicas are $resent and t!us $ossi*y

active to stimuate t!e immune system eit!er in isoation

or in com*ination %it! ot!er $!ytoc!emicas"

ong term treatmentof 0aediatricAIDS

with herbal remedies in ,omania

In 9omania& 10 c!idren ivin' %it! AIDS %!en

treated %it! natura !er*a remedies (!an Gai San)

s!o%ed im$rovement in D4 count& decrease in

mortaity rate and 'ood maintenance of quaity ofife"#!ese !eat! *enefits %ere s!o%n for t!ose %!o +e$t

ta+in' t!e !er*a medicines for 3 years& %it!out any

side-effect of t!e !er*a medicine usa'e"1E



&able 1+ Commonl* #sed herbs in HIV-AIDS treatment

S%in imm#nit* Circ#lator*stim#lantF Aloe $era (Aloe vera) F @in*er (Zingiber officinale)

Adatogen F @inG*o (Ginkgo biloba)

F @insen* (Panax s,) De#rativeF ?ithania (Withania somnifera) F @arlic (Allium sativum)

Anti-bacterialF @raefruit seed (Citrus , ereaist!

F 'roolis Diahoretic

Anti-inflammator*F /o>7ood ("uxus semervirens)

F Atract%lodes (Atract#lo$es macrocehala) Digestive carminativeF Cli$e tree (%lea euroaea) F 'eerint (&entha , ierita)

F "ea tree (&elaleuca alternifolia) .ectorantF "ureric (Curcuma longa) F H%sso ('#ssous officinalis)

Anti-viralactivit* He0ato0rotectiveF @olden Seal ('#$rastis cana$ensis)

F @reater celandine (Cheli$onium maus)F /iscuit root (omatium s*)

F iDuorice (Gl#c#rrhi+aglabra),

F Nee tree (A+a$irachta in$ica) F MilG thistle (-il#bum marianum)F St, John=s 7ort ('#ericum erforatum)

Anti-carcinogenF %er=s 7oad (.satis tinctoria)

Also denotes anti<$iral acti$it%,

Soe indications sho7n abo$e differ fro ".M theor%,

Adated fro (%ons et al, 200B),

&reatment with anti-o.idantherbs

ou$ed %it! immune status& anti-o,idant status

a$$ears to *e in+ed %it! ym$!ocyte eves in HIV"

In a 24-mont! $ros$ective study of 30 aduts %it!

sym$tomatic HIV and no anti-retrovira t!era$y& +!a+i

%eed Alternanthera pungens (A=) anti-o,idant !er*a

e,tract %as $rovided as a tea t!rice %ee+y (A= ?rou$)

vs" no tea contro (it!out A= ?rou$)"1 Venous *ood

sam$es reveaed reduced o,idative dama'e (i"e" as

evidenced *y reduced maondiade!yde concentration

and a reduction in advanced o,idation $rotein end

$roducts)& si'nificant increase ($ 0"001) of D4 and

DS ym$!ocytes and t!e ac+ of *ioo'ica !e$atic and

rena to,icity in t!e A= ?rou$"

idovudine (a nuceoside anao'ue reverse-transcri$tase in!i*itor) %as administered *efore and

after an American 'insen' e,tract (Pana uinue!olius)

%as administered to a study 'rou$ com$risin' of 10

!eat!y vounteers& for t%o %ee+s" #!e study found a

decrease in o,idative stress *iomar+ers (E2-iso$rostane

ratio I 0"<5C 0"<2-0"B at = 0"001 and B-!ydro,y-

deo,y'uanosine ratio I 0"<4C 0";5-0"52 at = I 0"02)

after 'insen' e,tract administration" E2-iso$rostane is a

meta*oite $roduced from t!e $ero,idation of essentia

fatty acids (7EA) ($rimariy arac!idonic acid)& %!ereas

B-!ydro,y-deo,y'uanosine is indicative of in vivo D8A

o,idative dama'e" #!e e,$eriment aso re$orted t!at'insen' e,tract did not interfere %it! $!armaco+inetics

of .idovudine" 1

$ental health benefits from herbal

medicine treatmentof HIV-AIDS

>enta !eat! is aso a +ey issue in HIV-AIDSsufferers& %!o are often sociay sti'matised" A study

conducted in #!aiand su''ested t!at !er*a medicines

can im$rove t!e menta !eat! as$ect of quaity of ife

(Jo) amon' HIV-AIDS infected su*ects" In t!is study&

132 HIV-$ositive aduts %ere 'iven a sef-administered

questionnaire to assess dimensions of $!ysica function

(=E) and menta !eat! (>H) in Jo" #!e data %as

aso coected on t!e use of !er*a medicine and socio-

demo'ra$!ic and $syc!osocia c!aracteristics reated to

HIV" Si'nificanty *etter >H %as o*served amon'

!er*a medicine users vs. non-users& %!ereas& !er*a

medicine did not !ave a statisticay si'nificant

association %it! =E scores" #!is im$rovement in >Hscore %as !i'!er amon' t!e sociay vunera*e

$o$uation"@ A $ace*o effect cannot *e rued out as a

cinica tria of s$ecific !er*a e,tracts %it! standardised

$!ytoc!emica concentrations is necessary to ma+e a

concusive recommendation on t!e use of s$ecific !er*a

medicine e,tracts in HIV-AIDS"

Actionof a derivative of St ohn3s wort

(Hypericum perforatum)

An isoated $rotein fraction& $2<(S)& derived from St

o!ns %ort (ypericum per!oratum) (usuay $rescri*ed

for de$ression and some anti-vira activity)& reducedt!e transcri$tion of t!e HIV-1 'enome in $rimary

cuture of micro'ia and astrocytes" #rans-Activator



of #ranscri$tion (#at) is a $rotein res$onsi*e for t!e

en!anced efficiency of vira transcri$tion (HIV dsD8A)

and causes a$o$tosis in #-ces t!us e,acer*atin'

HIV disease state" #!e $2<(S) is associated %it! t!e

transcri$tion factor /7G== and aso #at& c!an'in'

t!eir su*-ceuar ocation ( accumuation of /7G==

and #at in t!e $eri-nucear cyto$asmic com$artment)&affectin' D8A *indin' and !ence transcri$tiona

activity"21 In conunction %it! conventiona medication&

!er*a medicines $roved to re'uate transcri$tion

factors associated %it! HIV re$ication *ut aso

moduate immune function in HIV $atients" St o!ns

%ort traditionay is used for de$ression *ut aso s!o%s

efficacy as an anti-vira& $ossi*y via ateration of cyto$astic ocation of /7G= 2 and aso #at"

se of traditionalherbalmedicinewith

HIV-AIDS 0atientsin So#th

AfricaIn a descri$tive& $ros$ective and foo%-u$ study of33

HIV-$ositive $atients& t!e vira oad decreased and D4

counts increased after t!e consum$tion of traditiona

Sout! African !er*a medicines $rior to meas in

conunction %it! conventiona anti-retrovira dru's" #!e

$atients %ere a*e to increase t!eir socia activities suc!

as %or+ and !ad reduced $revaence of AIDS cac!e,ia"13

#!is su''ests t!at t!e com*ined t!era$y may *e usefufor

t!e treatment and mana'ement of immune su$$ression

and systemic infammation durin' HIV infection"

se of &C$ treatmentsfor HIV-AIDS

Studies !ave aso s!o%n t!at some #> !er*a

formuations are usefu in t!e mana'ement of HIV-AIDS

reated sym$toms"

val#ation of .iaomigran#les

ne e,$eriment evauated efficacy of ,iaomi 'ranues

(/0 KL3Af3) lycyrrhi +a glabra, Pinellia ternana ,

"cut ellaria baicalensi s, $odonopsis pilo sula, $opti s

chinensis, Astragalus membranaceus, $oi lacryma

%obi var" ma yuen, 1ithospermum s$$") in 40 HIV-AIDS

$atients %it! ora candidiasis" #!e study !ad t%o 'rou$sC

one treated %it! ,iaomi 'ranues (n M 40) and contro

'rou$ treated %it! anticandine" In *ot! 'rou$s t!ere %ere

im$rovements in sym$toms of ora 'reasy-stic+y& t!irst&

ast!enia& a*domina distension and anore,ia ($0"0;)"

om$ared to t!e contro 'rou$& t!ere %as si'nificant

im$rovement in sym$toms of ora 'reasy-stic+y and

t!irst in t!e ,iaomi 'rou$ ($0"0;)" 7fficacy rates %ere

aso muc! !i'!er in t!e ,iaomi 'rou$ t!an in t!e contro

'rou$ (50"06 vs" <2";6) and t!e 11"1 6 rea$se rate in

t!e ,iaomi 'rou$ %as o%er t!an t!e 31 6 in t!e contro"1

val#ation of Chinese herbal 0ills

In a dou*e-*ind $ace*o study of B HIV-infected

out$atients %it! a D4 ce count 0"; , 10(5)/& a

treatment usin' !inese !er*a $is %as investi'ated

for o*served c!an'es in HIV-1 98A $asma oads&

D4& DS ce counts and aso quaity of ife scores"

#!e $atients ta+in' !inese !er*s re$orted si'nificanty

more 'astrointestina distur*ances (<56 versus 3B6C $

M "003) t!an t!ose receivin' $ace*o& %it! no difference

in HIV disease $ro'ression"22 :t is %ort! notin' t!at t!e

aut!ors stated t!e *aseine eves of *ot! t!e contro and

treatment 'rou$ to *e equivaent& even t!ou'! t!emedian D4 counts %ere 2;6 o%er in t!e treatment

'rou$ at *aseine and t!e median HIV-1 $asma vira

oads 406 o%er& creatin' a +no%n *ias in t!e study"

val#ation of 5hong*an-4

Anot!er study e,amined t!e !inese !er*a

com*ination !on'yan-4 (N-4)& (iMAMiH:Af-46)C a !er*a

$rescri$tion containin' Oorean 'insen' (Pana ginseng),

astra'aus (Astragalus membranaceus) , 'oi *erry fruit

(1ycium barbarum), tric!osant!es root (&richosanthi s

2irilo3iii , !inese vioet (Viola mandshurica) and t!e

root of red-rooted sa'e or dans!en ("alvia miltiorrhi+a),

s!o%ed $ositive resuts" #!e randomised dou*e-*ind&

$ace*o-controed study conducted amon' <2 $atients

s!o%ed a ;6 increase in D4 vs" $ace*o (246

decrease)"23 #!e !er*s in N-4 are a +no%n for t!eir

ada$to'enic $ro$erties" At!ou'! t!e efficacy of 'insen'

!as not *een tested as a sin'e $rescri$tion in HIV& t!e

'insenoside 9!2& %!ic! is an active $!ytoc!emica in

'insen'& !as *een s!o%n to dis$ay immunore'uatory

and anti-infammatory $ro$erties in #-2 cesC and

t!e DS() cytoto,ic #-ce ine %!ic! !ave $rotective

effects a'ainst vira infection"24 :t %as o*served t!at

9!2-G 1 stimuated #-2 ce $roiferation and

aso IE8-y $roduction and t!us anti-vira activity&24

e,$ainin' $ossi*e anti-vira activity seen in t!e tria

usin' N-4" Sufated 1ycium barbarum $oysacc!arides

(sG=Ss) !ave *een s!o%n to increase cutured c!ic+en

$eri$!era ym$!ocytes" Eurt!er& an in vivo tria usin'

14-day-od c!ic+ens (nM 100) vaccinated %it! 8e%caste

disease vaccine s!o%ed t!at in t!e treatment 'rou$

t!e c!ic+ens inected %it! t!e various sG=Ss !ad

si'nificanty !i'!er ym$!ocytes $roiferation and

serum anti*ody titer&2; conferrin' immunoo'ica

moduatin' ca$a*iities" An et!anoic e,tract of Viola

mandshurica " Gec+er (V>) !as *een s!o%n in t!etreatment of *ronc!ia ast!ma in an ova*umin (VA)-

induced ast!matic GAG/c mouse mode to !ave

si'nificanty in!i*ited increases in tota immuno'o*uin

7 (I'7) and cyto+ines I-4 and I-13 eves in serum

and *ronc!oaveoar ava'e fuid (GAE)& and t!us may

*e of *enefit for #G-reated !y$ersensitivity of t!e un's

and *ronc!us"2 Severa e,tracts of "alvia miltiorrhi+a

(Dans!en) !ave *een s!o%n to dis$ay a neutraisin'

effect on enterovirus <1 induced cyto$at!ic condition in

Vero ces& r!a*domyosarcomaces (mai'nant tumour

from striated musce) and >9-; ces in vitro2< and

$er!a$s *e res$onsi*e for t!e anti-vira effect seen in $atients treated %it! N-4"



&able 2+ &ab#lation of literat#re search res#lts and differentiation 0rocess

Search &erm6s7

P Combinations

8o9 :#blications

6:#b$ed7

=H:&= ; =Herb= 11 106 7

=A:S=; =Herb= 4 61

=H:&= ; =Herbal= 60 449 27

=A:S=; =Herbal= 4 61 1B

=H:&=; =A:S=; =Herbal= 3 211 12

=H:&=; =A:S=; =Herb= 14 34

"otal Nuber of 'ublications 66

C$erlain* or eleted 'ublications 33

-e$ie7ed 'ublications 33

val#ation of fo#r

differentcombinations of &C$ herbsIn a study investi'atin' four different com*inations

of #> !er*s administered to 0 AIDS or AIDS-

reated com$e, (A9) $atients %!o %ere individuay

$rescri*ed one of four different com*inations of #>

!er*s& a decrease in vira oad& an increase in D4 and

an increase in #-ym$!ocyte counts %ere re$orted"@

:sin' a #> a$$roac!& $atients %it! AIDS or A9

%ere o*served to !ave 4de!iciencies4 of t!e un' or of

t!e s$een and stomac!C 4insu!!iciency4 of *ot! t!e s$een

and +idneys& or menta confusion due to $!e'm %it!

e,cessive !eat"@

val#ation of ;ian-%#n-ninA !inese !er*a formuation +no%n as 5ian2unnin

.Jt8f 8K1L)! %!ic! consists of 14 !er*s incudin' $optis

chinensis, astra'aus (Astragalus membranaceus),

asmine ('asminum o!!icinale), %ofi$oria fun'us

(6ol!iporia etensa) (syn" Poria cocos)& *ur-reed

("parganium stoloni!erum), Polygonatum odoratum

and "crophularia buergeriana is traditionay used for

its anti-infection& anti-tumour and immune-en!ancin'

$ro$erties" In in vitro trias& 5ian2unnin dis$ayed

HIV-'ro%t! in!i*ition and immunomoduation effects"

In a sin'e *ind $iot study over 24 %ee+s& t!is formua

si'nificanty decreased $asma virus oad at t!e end of %ee+s 12 and 24 ($ 0"01)& %it! increased $asma D4

count ($ 0"01) and %it! no adverse effects" =asma

virus oads %ere aso measured after four %ee+s from

ceasin' treatment& %it! vira oads sti o*served to *e

decreased" #!ese resuts su$$ort caims t!at 45ian7un8

9in4 !as t!e t!era$eutic $otentia to treat HIV-$ositive

$atients"2B

ne in'redient of 5ian7un9in: astra'aus

(A stragalus membranaceus) contains triter$ene

'ycosides ( e"'"& astra'aosides I-VII) and acts

as an ada$to'en and immune moduator" Eurt!ermore&

Polygonatum odoratum, contains sa$onin and favonoid

com$onents %!ic! e,!i*it *ot! anti-dia*etic effect and

anti-o,idant effects&25 and is traditionay used as a food

*y t!e 8u et!nic minority $eo$e of ="9" !ina"30 In

addition& "crophularia buergeriana (SG) moduates t!eimmune res$onses via cyto+ine $roduction" #raditionay&

SG %as used for fever and s%ein'& and in a !uman #-

ce ine (>#-4 ces)& mouse $eritonea

macro$!a'es cyto+ines %ere increased after e,$osure

to SG e,tract& via increase in t!e eve of intereu+in

(I)-2& I-4 and interferon (IE8)-y $roduction"31 #!us&

5ian7un9in contains !er*s t!at infuence D4 count

via immune moduation and cyto+ine $roduction& %!ic!

accords %it! its traditiona use"

Im0actof herbal medicineon adherence

to conventionatlhera0*

At!ou'! !er*a medicines are seen as A> t!era$iesin t!e est& in #!ird ord and deveo$in' nations& due

to t!e cost of conventiona anti-retrovira dru's& !er*a

medicines are a mainstay for t!e mana'ement and

treatment of HIV-AIDS" #%o studies e,amined t!e

im$act of com$ementary t!era$y on ad!erence to

conventiona t!era$ies32 and %!et!er t!e com$ementary

medicine !as an im$act on ad!erence to !i'!y active

anti-retrovira t!era$ies (HAA9#) amon'st HIV-

$ositive African- American %omen"33 #!e study incuded

3 %omen %!o %ere ta+in' one of t!e com$ementary

t!era$ies incudin' !er*a medicine at enroment"

omen %ere considered non-ad!erent if t!ey missedany dose of HAA9# in 30 days foo%in' *aseine"

Accordin' to a o'istic re'ression mode of assessment&

%omen on com$ementary medicine %ere 1"5 times

more i+ey to re$ort missin' t!eir dose of HAA9# over

t!e ast 30 days vs. %omen not ta+in' com$ementary

medicine"33 Simiary& erne%a et . al. 32 conducted a

study amon'st 1;2 HIV-$ositive atino 'ay and *ise,ua

men" In t!is t!e study& t!ose $atients usin'

com$ementary medicines %ere ess i+ey to attend t!eir

doctors a$$ointments& to foo% t!e advice of t!e doctors

or to ad!ere to $!armaceutica medicines $rescri*ed"32

In a study usin' a semi-structured intervie%er-administered questionnaire of Sout! African

individuas %it! HIV infection or AIDS& it %as reveaed



t!at a ar'e $ro$ortion of t!e $o$uation consut %it!

traditiona !eat! $ractitioners" Eurt!er & t!e maority

e,$erience ne'ative interactions %it! anti-retroviras

(A9Vs)" Interestin'y& !er*a $ractitioners (H=) %ere

intervie%ed& %it! 206 ma+in' a caim t!at t!ey %ere

a*e to cure t!e disease& %it! BB6 manufacturin' t!eir

o%n medications as aqueous $ant e,tracts" In addition&of t!e H=& ony 3B6 !ad received HIV-AIDS reated

trainin'& %it! many *eievin' t!at ony traditiona

and !er*a medicines s!oud *e used for HIV-AIDS

treatment& %!ie ot!ers *eieve t!ere is no !arm in

ta+in' *ot! concurrenty"34

Safet* and efficac*of herbs #sed in HIV-

AIDS treatment

#!ere are fe% cinica trias avaia*e usin' !er*s in

t!e co-treatment of HIV-AIDS" #!ere are aso a num*er

of safety issues re'ardin' co-administration t!at !ave

*een raised in t!e iterature"

Alternantherapungens

In a study of t!e use of Alternanthera pungens

!er*a tea t!e treatment of HIV& a si'nificant

decrease in $asma eves of *iomar+ers of o,idative

stress ($0"001) (A== and >DA) and a si'nificant

increase in D4 and DB ym$!ocytes ($0"001) %ere

s!o%n" #!ere %ere no to,icities reated to +idney or

iver in t!is

24-mont! $ros$ective study consistin' of 30 aduts %it!

sym$tomatic HIV and not receivin' HAA9#"1

ing*#an%ang

In a randomised dou*e-*ind tria ( mont!s)

on in'yuan+an' a$sue (NO) ; euco'en anao' ;

HAA9# dru's (nM;B) and euco'en ; NO anao' ;

HAA9# dru's s!o%ed t!at J increases eu+ocyte as

effectivey as euco'en ta*et"3; A ist of !er*s in t!is

formua is found in #a*e 3"

Chinese herbal 0ills

7ven t!ou'! t!e quaity of ife %as im$roved in many

of t!e studies invovin' t!e use of !er*a medicines in

HIV-AIDS& in some instances it may $ose a ne'ative

effect" In a $ace*o-controed dou*e-*ind study of a

!inese !er*a medicine (un-named $ractitioner devised

$i com$risin' of 3; !inese !er*s) %!ic! %as caimed

to reduce t!e sym$toms and aso to im$rove t!e quaity

of ife for HIV-infected $ersons over mont!s" A

num*er of t!e !er*a s$ecies are aso used in estern

!er*a medicine" #!e ar'e maority of actions dis$ayed

*y t!e ist are reated to t!eir anti-o,idant action

#!e formua contained t!e foo%in' !er*s

Iin'.!i or reis!i (anoderma lucidum), %oad (Isatis

tinctoria ), >iettia reticuate& astra'aus (Astragalus

membranaceus), Sno% fun'us (&remealla !uci!ormis),

Andro'ra$!is (Andrographis paniculata) , a$anese!oneysuc+e (1onicera%aponica) , a'ar%ood

(Auilaria agallocha) , !orny 'oat%eed (Epimedium

macranthum),

odenandia ( ldenlandia di!!usa ), cistanc!e (

$i stanche salsa) , #i*et 'oi *erry (1ycium chinen se) ,

sea tan'e (1aminaria %aponica), don' quai (Angelica

sinensis), a$anese +not%eed (Polygonum

cuspidatum),American 'insen' (Pana ,uin,ue!olius) ,

sc!i.andra ("chirandra chinensi s ), !inese $rivet

(1igustrum lucidum), Gai !u (Atractylodesmacrocephala ), re!mannia (Rehmannia glutinosa),

dans!en ("alvia miltiorrhi+ai, tumeric ($urcuma

longa) , vioet !er* (yedoensi s ), >andarin oran'e

( $itrus reticulatereticulata ), $aeonia (Paeonia

lacti!lora) , $oy'onum (Polygonum multi!iorum),

eucommia (Eucommia ulmoides), amomum

(Amomum villosum ), !inese iquorice

(lycyrrhi+a uralensis ), sef-!ea (Prunella vulgari s ) ,

cordyce$s ($ordyceps sinen sis) , $atc!oui $ant

(Pogostemon cablin), a$anese !a%t!orn ($rataegus

cuneata), Massamedicata!ermentata , *arey (ordeum

vulgare), rice ( ry+a sativa) %it! fiers suc! asmicrocrystaine ceuose (fier)& ma'nesium stearate

(anti-ad!erent)& siicon dio,ide ( desiccant)& and 'um

acacia" Interestin'y& 'astrointestina distur*ances

%ere t!e ony effect of t!is !inese !er*a mi,ture

%it! no si'nificant differences in $asma vira oads&

D4 counts& sym$toms& and $syc!ometric $arameters

or HIV-1 98A eves"122

I<$-1

In a fuy-randomised& dou*e-*ind $ace*o&

cinic-controed study revie%in' t!e s!ort-term (12

%ee+) safety and efficacy of a !inese medicina !er*

$re$aration (I?>-1) to treat HIV& t!ere %as reveaed

no si'nificance differences *et%een t!e $ace*o and t!e

!inese !er*a medicine e,ce$t for some reduction in

sym$toms (i"e" ife satisfaction& $erceived !eat!& socia

function& and menta !eat!)"36 #!e s$ecies $resent

in t!e !inese I Oam$o medicina !er* $re$aration

incuded !er*s $re$ared *ased on AIDS sym$tomoo'y"

f 31 !er*a in'redients in t!e ;0-m' ta*et& t!ose

$resent in si'nificant concentration incuded in'.i or

reis!i ( anoderma lucidum), %oad (Isatis tinctoria

), astra'aus (Astragalus membranaceus), andro'ra$!is

(Andrographis paniculata), a$anese !oneysuc+e

(1onicera %aponica), ever'reen %isteria (Milletiareticulata), odenandia ( ldenlandia di!!usa ),

and das!i +om*u (1aminaria %aponica). #!ese !er*s

!ave a ran'e of immunomoduatin'& anti-vira& anti-

cancer $ro$erties" 7ven t!ou'! t!ere %as an

im$rovement in sym$toms& t!is aone coud not *e

inter$reted as a on' term success %it! t!e use of t!is

s$ecific !inese >edicine I Oam$o !er* formuation as

$resented for t!e treatment of HIV" >easures suc! as

quaity of ife can *e su*ective and o$en to *ias suc!

as $ace*o effect" Actua im$rovements in quantitative

$arameters suc! as D4 counts %ere not recorded

and/or not si'nificant and t!us it is un+no%n %!et!er immune function !ad *een affected or im$roved"



&able '+ Details and ma=oro#tcomesof reviewed research articlesand e0idemiologicasl t#dies

Abbreviations+ A:S8 AcDuired :unodeficienc% S%ndroe A-.8 A:S<related cole>! A-"8 Anti<retro$iral treatentthera%!

H8 Heres Ooster (Shin*les)! HAA-"8 Hi*hl% Acti$e Anti<-etro$iral "hera%! NAS8 No ad$erse side effects! '&8 lasa $iral

loads! "/8 "uberculosis! t I ; < increaseNdecrease! '*'8 '<*l%corotein,

Herbal Secies Ar5ano$a et al,L 200 Cen label stud% A (n I 20) and

/ (n I 20)<"/H:&

first<line anti<"/ thera%

(A"") or A": ; luno>el

(Oherelo)! resecti$el%

Oherelo had ositi$e iact on the

"/ dru*s and it ; incidence of ne7

oortunistic infections

/lonG et al,45 2012 Cen<label!

randoised! t7o<

eriod! crosso$er

hase : trial

1E health%

$olunteers

Ginkgo bi.oba e>tract;ralte*ra$ir

Althou*h there 7as ar*inal

increase in .a> of ralte*ra$ir! it 7as

of inor si*nificance,

/uracG et al,3 16 -andoised

controlled trial

30 Adults 7ith

s%toatic

H:&

'rearation of 31 .hinese

herbs

:ro$eents in Dualit% of life and

s%tos

No chan*e in .4; count

.olebunders

et al,4

2003 "7o Duestionnaire

based sur$e%s

uroean

oulation

Assessed the use of anti<

retro$irals! coleentar% or

alternati$e edicines

&itainsinerals 7ere ost

coonl% used follo7ed b%

hoeoath% and herbal roducts,.oleentar% edicines are

coonl% used desite a$ailabilit%

of haraceutical edicine,

5ohan et al,1 200 24 onth

rosecti$e stud%

30 Adults 7ith

s%toatic

H:&! no A-"

Alternanthera ungens

(GhaGi 7eed) e>tract as drinG

tea anti<o>idant containin*

herbal e>tract) thrice 7eeGl%

or lacebo

; o>idati$e daa*e! t T-.4 and

.E l%hoc%tes (0,001)

No heatic and renal to>icit% in A'

*rou

u**an et al, 3 2001 Sur$e% (#SA

based)

11<H:&

ositi$e out<

atients

#se of $arious herbal

edicines sur$e%ed and

recorded

6PQ used .AM at soe oint of

tie

40Q 7ere recei$in* .AM at the tie

of sur$e%,

>ercise(43Q) 7as the ostcoon .AM used follo7ed b%

lifest%le chan*es! dietar%

suleents! counsellin*! herbal

edications! e*a$itains!and

ra%er thera%,

P4Q used a rotease inhibitor

edication! 1BQ used a rotease

inhibitor sarin* re*ie! and 11 Q

had no current or rior anti<

retro$iraluse,

Han1; 200P &arious

treatents

60 cases of

A:S or A-.

our different ".M forulae

deendin* on resentation,

E6,PQ atients ; $irus loadin*

t .4 " l%hoc%te count,

Henness% et

al,4s

2002 0,1BQ St John=s

?ort! 600 *thrice dail% 16

da%s

nI1B SJ?

nIP lacebo

St John=s 7ort ('#ericum

erforatum)

t '*' e>ression (4,2 fold) fro

baseline in SJ? *rou! e$idenced b%rhodaine efflu>,

'*' efflu> 7as inhibited in both

*rous b% -itona$ir (B RM),

Herrera<

Arellano et al, 5200 .ross<sectional

stud% of H:&

atients I sur$e%,

23 #se of $arious herbal


recorded

2,PQ usin* herbal edicine

ercei$ed benefit of Dualit% of life

Hos% et al,11 1 Non<randoised!

non<lacebo

controlled!

obser$ational

stud% (2 hases),

'hase 18 3 o

follo7 u! 'hase

28 3 o follo7 u,

'hase 18 B2

cc

'hase 28 1B4

cc

Herbal treatent accordin*

to healers= rescritions

'hase 18 H suer<infection (1EQ $s,

42Q! 0,02) and Geloid foration

less coon in herbal edicine $s,

control,

'hase 28 aster ain resolution 7ith

herbal atients $s, control,



&able '+ Details and ma=oro#tcomesof reviewed research articlesand e0idemiologicaslt#dies (cont.)

Herbal Secies

JandoureG etal,43

1E 'rosecti$e!

sin*le centre!

oen<labelled

stud%

12 atients

7ith A:S

and oral

candidiasis

1Bl "ea tree oil

(&elaleuca alternifolia)

oral solution four ties

dail%

At 2 7eeGs8 P iro$ed! none 7ere

cured and B 7ere unchan*ed,

At 4 7eeGs8 E resonded (2 cured

and 6 iro$ed)! 4 did not resond,

P atients sho7ed %colo*ical

resonse,

Jerne7all et al32 200B Sur$e% 1B2 H:&<

ositi$e

atino *a%

and bise>ual

en

#se of $arious herbal


recorded

E0Q reorted to use .AM,

Asian .AM and herbal edicines

coonl% used, Adherence to

haraceutical treatent 7as lo7er

in those usin* .AM,

Jian* et al,16 200 Cen label

inter$entional

stud% (@r A8

anticandine!

@r /8 >iaoi

*ranules)

n I 40

atients I

*rou

/iaomi granules(( f012JJMfifl,)8

Gl#c#rrhi+a glabra) ( tt 3 ))

Pinellia ternana2

-cutellaria baicalensis( 4( 4f* )

Co$onosis ilosula (=Jt)

Cotis chinensis( 4i a )

Astragalus membranaceus(JiNM)! Coix lacr#ma5obi

var* ma#uen (C11#)QRM)&

ithosermum s* ( 33 )

Anticandine (anti< candidiasis

haraceutical)

"here 7as iro$eent in

s%tos of oral *reas%<sticG%!

thirst%! asthenia! abdoinal

distension and anore>ia in both

the *rous, Cral *reas%<sticGiness !

thirst% and relase rate 7ere better in

>iaoi *rou vs* control *rou,

Jian* et al,3B 2011 -andoised

double<blind trial

(6 onths)

Jin*%uanGan*

.asule (Abbre$,

J+) (lBiMJlJ1Jt)

n I BE

"reatent (")

n I BE .ontrol

(.)

(") Jin*%uanGan* .asule

(lJBiMJlSl=>=8ii)

Panax ginseng( 67*3 )

Astragalus membranaceus

(JiNM)

igustrum luci$um (--A," #58*9 -Mf )

:ioscorea oosita( ' % SLJ);ehmannia glutinosa (root) (

MilS) Ammomum s fruit

.li=J81I) <ime$ium s, T1 UK818)

Angelica sinensis (3 +,3)

euco*en analo*

and HAA-" dru*s

(.) euco*en(euco*en)

and HAA-" dru*s

J+ enhances leuGoc%te le$el as

effecti$el% as euco*en tablet (*rade

:! 11 leuGoenia)! V euco*en (*rade

:ll leuGoenia), NAS,

Note8 both *rous 7ere on HAA-"

isan*au eta1,10

200P Sei<structured

Duestionnaire

30 herbal

ractitioners

&arious African herbal

edical secies described,

Most coon H:&<A:S

oortunistic infections 7ere "/ and

oral candidiasis

usu et al,3P 2004 Cen<label stud% 2E Gl#c#rrhi+a glabra

Artemisia caillaris

&arus alba

Astragalus membranaceus

Carthamus tinctorius

-eduction of lasa H:&<1 -NA iV 0,B lo* (treatent) and follo7 ueriod 4<10 (14,2<3B,PQ), Ne*ati$e

resonse t lasa H:&<1 -NA V 0,Blo* 7ere 2<4 (0<14,2Q),

No t .4 cell count,

ee et al,1A 200E 'haracoGinetic

stud%

1 C health%

$olunteers

300 * Oido$udine orall%

before and after 2 7eeGs

of treatent 7ith

Aerican *insen* (Panax

=uin=uefo.ius) e>tract 200

* b,i,d,

@insenosidedoes not alter theharacoGinetics of Oido$udine,

i o>idati$e stress bioarGers

T2<isorostaneratioI 0,P 0,P2<0,E6

,001M E<h%dro>%<deo>%*uanosine

ratio I 0, P4M 0,B<0,2M I0,02),

MaeG<a<nanta7at etal,3s

2003 'rosecti$e oen

stud% (6 onth)

21

as%toatic

H:& atients

Jin Huan* corises of

Curcuma longa2 artificial

Calculus bovis2 Panax

notoginseng 2 Aucklan$ialaa2 ;heum* officinale2

>ritillaria cirrhosa2/orneolu S%ntheticu

No chan*es to $iral load or .4

count

Ad$erse reactions increased bo7el

o$eents! $a*ue taste,




Herbal Secies

MaeG<a<

nanta7at et

al,L

200 Cen<labelled

trial

1E

as%toatic

H:& atients

./M<A01! a .hinese

herbal edicine forulation

coosed of Panax

ginseng -chisan$ra

chinensis2 Zi+ihus uube2

Crataegus innatifi$a2

?igna ra$iata2 Gl#cine

max2

-accharom#ces cerevisiae2

No si*nificant chan*es in lo* $iral

load or .4 cell counts

Ad$erse reactions interittent

diarrhoea! sGin rashitchin*!

increased bo7el o$eent

Mbah et al,41 200P lnter$entional

stud%

60 H:&<A:S

atients

Acetone<7ater A+a$irachta

in$ica (nee) leaf e>tract

(:-A/)

B0Q had si*nificant (1BQ) increase

in ean .4 cells i5@ 0,001),

Molt6 et al,4P 2012 Cen<label! fi>ed<

seDuence stud%

1B H:&

infected

atients

1B00*d <chinacea

ururea root and 400*

etra$irine,

@eoetric Mean -atio of etra$irine

co<adinistered 7ith E. ururea I

1,0PM safe for co<adinistration,

Molt6 et al,46 2011 Cen<label! fi>ed<

seDuence stud%(4 7eeGs)

1B00*d <chinacea

ururea root and 200*

daruna$ir<ritona$ir (rotease

inhibitor)

Herbal edicine co<adinistered

7ith daruna$ir< ritona$ir resulted in

sli*ht decrease in the concentration

of daruna$ir

C7en<Sith etal,33

200P Cbser$ational

stud%

366 H:&<

ositi$e!

ostl%

African<

Aerican

7oen! a*ed

1E<B0 %ears

.AM (.hinese herbs!

ushroos! *arlic! *insen*

or al*ae or ulti$itains or

reli*iouss%chic health or

bod%7orG) use and HAA-"

adherence aon* H:&;

7oen

?oen usin* .AM 7ere 1,6 ties

ore liGel% to reort issin* HAA-"

doses

Su*ioto eta1,20

200B Sur$e% 132 H:&<

ositi$e "hai

adults

Herbal edicine Si*nificant iro$eent in ental

health but no effect on h%sical

health,

"ani et al,1E 2002 on* ter stud%

7ith herbalinter$ention (%ear

12<2000)

10 children

7ith ediatric A:S

.han /ai San < a

forulation of 30 herbsundefined

:ro$eent in .4 counts!

ortalit% rates and Dualit% of life,"reatent sho7ed ositi$e results

after 1 to 3 %ears and du* resistant

H:& strains did not eer*e

"shiban*u etal,13

2004 12<onth

follo7<u stud%,

33 H:&<

ositi$e

atients

"raditional South African

herbal edicines undefined,

Anti<$iral acti$it% resent

&anlandin*ha

et al,12

2006 Anal%sis of data

collected durin*

the %ear 2000

412 H:&<A:S

atients

/itter .ucuber (&omor$ica

charantia) and other secies

used

P4Q reorted usin* alloathic

edicine 7ith 31 Q reorted usin*

herbal treatents (3Q o$erla)

&aODueO et al,42 2002 'rosecti$e!

sin*le<centre!

oen<label stud%

2P A:S

atients 7ith

oral candidias

Alcohol<based or alcohol<

free &elaleuca alternifolia

oral solution

60Q of atients sho7ed clinical

resonse in 4 7eeGs,

?al7%n et al,34 2010 Sei<structured

Duestionnaire

Herbal

ractitioners

&arious aDueous lant

e>tracts

Cnl% 3EQ had recei$ed H:&<A:S

related trainin*

?an* et al,23 2006 -andoised

double<blinded

and lacebo<

aral: el<control

led trial

P2 atients

di$ided into

treatent

(nI36) and

control (nI36)

hon*%an<4 (+<4)! a

.hinese herbal rearation

t .4 count (+<4)*rou (BQ) $s,

24Q ; in lacebo *rou, t .(4B)

-A(;)! W .(E)(;)count! H:& $irusload! W t b,7,

?eber et al,22 1 'rosecti$e!

lacebo<

controlled

double<blind

stud% (6 ths),

6E H:&<

infected

adults

4 > P ills dail% containin* a

standardised rearation of

3B .hinese herbs (listed in

te>t abo$e) $ersus lacebo,

Ad$erse reactions *astrointestinal

disturbances,

No si*, t H:&<1 -NA le$el!

'&! .4 cell counts!

s%choetric

araeters,

Median .4 cell counts ( ; 0,0B >




Herbal Secies

?u5is*ulen* et 2012 thnobotanical na Pol#gonatum macroo$ium2 aten as salad! *reen tea ethanolal,3o re$ie7 P c#tonema2 P filies e>tract is used as adato*en, :n

".M P o$oratum reinforces LDiL!

nourishin* L%inL and oistenin* the

lun*s! stren*thenin* Gidne% and

sleen

han et al,2B 2000 'ilot stud%! sin*le E atients Xian<Gun<Nin casules Si*, t lasa $irus load 7eeG 12 Wblind lacebo Cotis chinensis 7eeG 24! W V4 7eeG after cessationstud% (24 7eeGs) Astragalus membranaceus2 of treatent cf" baseline,

Gar$enia asminoi$es2 t blood .4 cell counts! W NAS

Poria cocos! -arganium

stoloniferum

>ral s#sension SH

A study *y Ousum et a3< %!o e,amined ora

sus$ension SH& a com*ination of five !inese !er*s&

native to Asia& near-Asia and 7uro$e" #!ese !er*s&

namey icorice ( lycyrrhi+a glabra ), ca$iary%orm%ood (Artemisia capillaris) %!ite mu*erry

(Marus alba), astra'aus (Astragalus membranaceus ),

saffo%er ( $arthamus tinctorius) %ere eit!er $rovided

as ;' soid or 30 m tincture& divided into t!ree doses

daiy" #!ese !er*s !ave $!ytoc!emicas $resent t!at

dis$ay efficacy as anti- infammatory& adrena tonic&

anti-o,idant& anti-vira& immune en!ancement&

ada$to'enic and $ost$randia" #!e com*ination %as

administered daiy in t!ree divided doses $ost-mea

amon'st 2B su*ects %it! HIV-

AIDS" #!e $artici$ants aso received sufamet!o,a.oe/

trimet!o$rim (anti*iotic $!armaceutica seectivea'ainst Pneumocy stispneumonia in $atients %it! HIV)&

400/B0 m' after *rea+fast %it! treatment $rovided for

12 %ee+s" #!e com*ination %as s!o%n to *e safe and

s!o%ed satisfactory outcomes in terms of vira oad&

%!ereas immunoo'ica res$onse measured in terms

of increase of D4 ce count did not demonstrate a

satisfactory outcome"3<

in H#ang

in Huan' a !inese !er*a medicine com*ination

s!o%ed no anti-vira effect at!ou'! $atients descri*ed

a certain im$rovement in $ersona %e-*ein'"3B Suc!

measures as %e-*ein' are su*ective and o$en to *iason t!e $art of t!e o*server&35 !o%ever in t!e conte,t of

t!e #> o*ective to re-*aance t!e !eat! status of

t!e $atient t!ere is room in t!e treatment mana'ement

for a $ace*o-i+e effect of t!e qi& an unquantifia*e

com$onent& simiar to vis medicatri naturae. #!is

re-*aancin' $rocess is not readiy transated into

numerica terms& so #> utiises quaitative descri$tions

to c!aracterise !eat! status" #!e formuation of in

Huan' com$rises of turmeric ($urcuma longa), artificia

cacuus *ovis (i"e" dried o, 'astonesC c!oestero/

*ie sats)& tien-c!i 'insen' (Pana notoginseng) , mu

,ian' (Auc2landia =appa), Rheum o!!icinale, fritiaria(-ritillaria cirrhosa ) , *in' $ian (Gomeoum

Synt!eticum)

as s!o%n in #a*e 3& and t!e in'redients a$$ear to !ave

anti-infammatory and anti-o,idant actions"

C)/$-A01

vera& t!e $eer-revie%ed iterature su''ests t!ate,ce$t for Jian-Oun-8in& various !inese !er*a

medicine formuations s!o%ed no& or ony imited&

effectiveness for t!e treatment of HIV-AIDS& %it! some

dis$ayin' adverse effects" #!is %as aso s!o%n in a

study on t!e use of a !inese medicina com*ination

+no%n as OG>-A& %!ic! !ad no effect on D4 ce

counts or HIV vira oadin'& *ut !ad im$rovement in

cod and fu sym$toms su''estin' an immune-

stimuant effect& *ut %it! intermittent diarr!oea

o*served in over !af of t!e $atients& to'et!er %it!

s+in ras!es and increased $eristasis as side effects"@

8eem eaf

A study@ assessed t!e efficacy of a neem eaf e,tract

(A+adirachta indica) amon'st 0 HIV-AIDS su*ects

(HIV I or II $ositive& D4 ce count 300 ces/& and

anti-retrovira naive)" #raditionay A. indica !as *een

used& amon'st ot!er actions& for its anti-vira activity"

In a study& t!e effect of an acetone-%ater neem eaf

e,tract (I9AG)& of 1"0 ' daiy for 12 %ee+s& on immunity

and vira oad %ere monitored" f t!e 0 $artici$ants&

;0 (B3"336) %ere com$iant" #!ere %as si'nificant

im$rovement in D4 ce count in t!ese ;0 $atients

($0"001) at 12 %ee+s" #!ere %as im$rovement in t!e

eryt!rocyte sedimentation rate ( 4 mm/!r at *aseineto 1 mm/!r at %ee+ 12)" #!ere %as aso a decrease in

HIV-AIDS-reated $at!oo'ies (120 at *aseine to ; at 12

%ee+s)" Eurt!er& t!ere %as a si'nificant increase in mean

*ody%ei'!t& !aemo'o*in concentration and ym$!ocyte

differentia count o*served" 8o maor adverse effects

%ere re$orted in t!e study"41

$elale#ca

#%o studies evauated t!e efficacy of oi derived

from t!e 'enus meaeuca in fucona.oe-refractory

(anti-fun'a $!armaceutica resistant) ora candidiasis

amon'st AIDS $atients"42T

43

An aco!o-*ased and



aco!o-free meaeuca ora soution %as evauated

for t%o to four %ee+s amon'st AIDS $atients %it!

fucona.oe-refractory oro$!aryn'ea candidiasis

(%it!in mout! cavity) in a $ros$ective& sin'e-centre&

o$en-a*e study"42 #%enty-seven $artici$ants randomy

received eit!er aco!o-*ased or aco!o-free meaeuca

ora soution four times daiy at a 1H 1 e,tract ratio"#!e $rimary study aim %as t!e resoution of cinica

esions" 7vauation of cinica si'ns and sym$toms of

ora candidiasis and quantitative yeast cutures %ere

In a revie% of HIV-infected individuas& seenium %as

su''ested to *e *eneficia due to its in!i*itory effect in

HIV in vitro and for increasin' D4 counts in vivo, and

it !as *een o*served as a deficient nutrient in co!orts

%it! HIV infection"4; #!us& *ra.i nuts (#ertholletia

ecelsa), and *urdoc+ root (Arctium s$$")& %!ic! contain

!i'!er eves of seenium& may *e a *eneficia incusionin t!e diet of HIV-AIDS sufferers"

Im0actof CA$ on the 0harmaco%ineticsof $erformed at t%o and four %ee+s" At %ee+ four& cinica conventiona

mledicine

res$onse %as demonstrated in 06 of t!e $artici$ants

su''estin' efficacy in ora candidiasis refractory to

fucona.oe in AIDS $atients"42 Eurt!er & in a $ros$ective&

sin'e-centre& o$en-a*eed study (no *indin') %!ic!

evauated 12 $atients %it! AIDS and ora candidiasis

resistant to fucona.oe"43 #!e $atients %ere treated

usin' a 1; m meaeuca ora soution four times a day&

administered as a mout! %as!& for a $eriod of t%o to

four %ee+s" #!e $artici$ants %ere evauated %ee+y

*ot! cinicay and %it! quantitative yeast cutures" A

tota of B of t!e 12 $atients res$onded $ositivey in four

%ee+s (2 cured& im$roved %it! 4 not res$ondin') to

t!e $rescri*ed t!era$y" Seven $atients s!o%ed

mycoo'ica res$onse" inica rea$se %as not o*served

amon'st cured $atients durin' a foo%-u$ of t!e

co!ort after a t%o to four %ee+ $eriod after fina

evauation"43

Americanginseng

Heat!y $atients consumin' 200m' of a 'insenoside-enric!ed American 'insen' (Pana uinue!olius)

e,tract for t%o %ee+s !ave *een o*served to induce

$!ase 2 (i"e" :D=-'ucuronosytransferases&

sufotransferases& 8-acetytransferases& 'utat!ione S-

transferases and met!ytransferases) and antio,idant

en.ymes in vitro and t!ou'!t to increase t!e cearance

of .idovudine& an anti-retrovira dru' at a 300 m'

dosa'e"15 earance is t!ou'!t to *e due to increased

quinone reductase activity" Ho%ever t%o %ee+s of t!e P.

uinue!olius e,tract inta+e did not adversey ater

.idovudine $!armaco+inetics& *ut %as s!o%n to reduce

o,idative stress mar+ers& and t!us a $ositive outcome

for treatment of HIV-AIDS $atients usin' t!e e,tract for

its $resumed ada$to'enic $ro$erties"15

$icron#trients

Interestin'y& in a study of su*-Sa!ara African HIV-

$ositive $atients& it %as o*served t!at micronutrient

deficiencies (i"e" micronutrients incudin' vitamins

A& & and 7& K-carotene& seenium& .inc& and food/tea

$oy$!enos) are common" Due to HIV infection& t!ere

is an increased 'eneration of reactive o,y'en s$ecies

(9S)" #!ese anti-o,idant nutrients can *e $rovided via

an anti-o,idant ric!-diet (i"e" fruit and ve'eta*e *ased

diets) or via dietary anti-o,idant su$$ements and may!ave a $ositive effect on D4 and vira oad in HIV-

$ositive $atients t!at are inei'i*e for anti-retrovira

t!era$y"44

In traditiona estern !er*a medicine St o!ns

ort (ypericum per!oratum) is used for t!e treatment

of mid de$ression and Echinacea s$$" for t!eir

immunomoduation action"

In a study investi'atin' t!e safety of t!e use of

ec!inacea (Echinacea purpurea) and its interaction

%it! etravirine (non-nuceoside reverse transcri$tasein!i*itor of HIV)& $atients received 400 m' once daiy

of etravirine and aso E. purpurea root (;00 m' every B

!) over a 14 day $eriod" #!e etravirine $!armaco+inetic

$arameters suc! as 'eometric mean ratio s!o%ed t!at

t!e co-administration of E. purpur ea %it! etravirine %as

safe and %e-toerated in HIV-infected $atients"4 #!is

o*servation %as aso noted in a study of co-

administration of E. purpurea %it! darunavir-ritonavir

($rotease in!i*itor& anti-retrovira dru')& *ut t!ere %as

a minor decrease in darunavir concentrations& %!ic!

%arranted t!e monitorin' of darunavir concentrations in

$asma to ensure t!e $atient %as receivin' adequatedosa'e"4<

onversey& St o!ns %ort (ypericum per!oratum)

!as *een s!o%n to increase t!e activity of $-'yco$rotein

(='=)& %!ic! is a trans-mem*rane $rotein t!at e,cretes

,enoto,ins (i"e" $!armaceutica com$ounds or t!eir

conu'ates) from ces suc! as anti-vira conu'ates&

es$eciay indinavir and cycos$orine %!ic! are +no%n

su*strates for cytoc!rome =4;0 3A4 (N=3A4)& and

%!ic! t!eoreticay may $ose a t!reat to t!e efficacy of

an anti-retrovira dru'" Anot!er $ace*o-controed study

aso s!o%ed utiity of St o!ns %ort to increase ='=

e,$ression (4"2 fod) from *aseine"4B#!e co-administration of in2go biloba e,tract

mar'inay increased cma, (ma,ima $asma dru'

concentration in a tested area $ost-administration) of

rate'ravir& !o%ever t!ere %as no effect on rate'ravir

e,$osure" #!e c!an'e in 111a, of rate'ravir %as

considered of minor si'nificance o%in' to t!e ar'e

inter- su*ect varia*iity ofrate'ravir"45

#!us& some !er*a medicines a$$ear to *e safe

for co-use %it! anti-retrovira medicine& and $rovide

immune-su$$ortive action in t!e treatment of HIV-AIDS

and $resent a vaua*e com$ementary treatment o$tions

for $atients& *ut t!ere are sti questions a*out ot!ersdue to $ossi*e interaction %it! anti-retrovira dru's and

reduction in t!eir efficacy i"e" reduction of cma,U



Concl#ding remar%s

Her*a medicines are commony used a over t!e

%ord in *ot! deveo$in' and deveo$ed countries&

es $eciay in t!e mana'ement of c!ronic conditions"

#!ey are used for t!e treatment of HIV-AIDS and

associated conditions suc! as o$$ortunistic infections"

7mer'in' evidence su''ests some *enefits of !er*amedicines for immune moduatin' effects& *ut t!ere are

some concerns reated to its use for e,am$e t!e

$ossi*e reduced efficacy of antiretrovira dru's" Her*a

medicines may *e suited to immune-su$$ort *y

increasin' D4& rat!er t!an treatment of HIV-AIDS"

Ho%ever& t!ere !ave not *een an e,tensive num*er

cinica trias (i"e" randomised cinica trias) carried out

on t!e utiity of !er*a medicine as a direct treatment or

in com*ination %it! anti-retrovira dru's& as reveaed in

our iterature searc! for t!is revie%"

Studies indicate t!at some !er*a medicines (sin'e

e,tracts and com*ination formuas) are safe andefficacious !o%ever in some instances safety issues

arose& es$eciay in reation to t!e a*iity of $ractitioners

to administer a $!ytoc!emicay reevant !er*a e,tract

or mi,ture" #!ere is aso t!e dan'er of contamination or

aduteration %it! ot!er materias suc! as !eavy metas&

$esticides& *acteria or $!armaceutica com$ounds %!ic!

is a +no%n concern for !inese !er*a medicines" Some

studies s!o%ed efficacy of !er*s in terms of

immunoo'ica $arameters& vira oad and

sym$tomatoo'y !o%ever since t!e studies %ere not

conducted on ar'e $o$uations and %ere not of a

on'itudina co!ort desi'n& t!ey are not concusive

enou'! to create a definitive ans%er reatin' to t!e use of

!er*a medicines in HIV-AIDS"

#!e main actions of !er*a medicine for t!e treatment

of HIV-AIDS are via immune moduation& anti-o,idant

activity and some anti-retrovira activity of isoated

fractions" onsiderin' t!e $rimary evidence of efficacy

from t!ese sma trias& and aso seected in vitro ce

cuture& conductin' furt!er in vitro for mec!anistic

understandin'& as %e as cinica studies may *e

*eneficia and may ead to a cearer recommendation on

!o% and %!ere in t!e treatment $an to use !er*a

medicines in HIV-AIDS treatment" Eurt!er &

standardisation of e,tracts and vaidation usin' dou*e- *ind cinica trias are required %it! formaised

com$ementary treatment $rotocos co-administered

%it! anti-retrovira dru's"

Anot!er issue t!at %as reveaed in t!is revie% is t!e

si'nificant incidence of $eo$e %it! HIV-AIDS usin'

!er*a medicine and not ad!erin' to conventiona

medica treatment" #!is may *e due to com$iance

issues or t!e avaia*iity and cost of modem anti-

retrovira dru's" #!us& t!ere is a need to educate $atients&

as %e as !er*a medicine $ractitioners across t!e 'o*e&

of t!e im$ortance of conventiona medicine and t!e need

for e,tensive study of !er*/dru' interactions" !inese!er*a medicine& usin' com*inations of u$ to 40 !er*s&

'ave resuts su''estin' minima success ot!er t!an

immune su$$ortive functions& as did African !er*a

medicine" In t!ese traditiona

systems of medicine& %!ic! aso a$$ear as art forms

rat!er t!an scientific $ractices& t!e $ractitioner reies on a

static em$irica *eief system %it!out considerin' a

scientific understandin' of t!e $atients !eat!"

onversey& t!is is aso true of $!armacoo'ica

intervention of HIV-AIDS" #!e main focus of traditiona

systems is to re-*aance $atient !eat! and *odiysystems rat!er t!an to contro or im$ede vira activity"

Simiary& estern !er*a medicine& *ot! traditiona and

modem (as $!armaco'nosy)& a$$ears to *e of *enefit in

immune su$$ort rat!er t!an curin' t!e condition per se.

inica trias usin' $!ytoc!emicay vaidated !er*a

medicines in conunction %it! $!armacoo'ica

intervention suc! as anti-retroviras are required to

assess $otentia *enefits in suc! a com$e, condition

%!ic! often !as many confoundin' co-mor*idities"

#!ere is $otentia for an inte'rative medicine system&

ena*in' t!e $atient to eect for eit!er sin'e or

com*ined treatment from a $!armacoo'ica&

$!armaco'nosy and traditiona $ers$ective and to incude

muti$e modaities in t!e treatment $an %!ic! %oud

incude t!e use of !er*a medicines"

In concusion& !er*a medicines are %idey used in t!e

treatment of HIV-AIDS and associated conditions" #!ere

are studies su''estin' t!e safety and a de'ree of efficacy

for some !er*a medicines %it!& some studies su''estin'

a $ositive im$act on vira oad and immunoo'ica

$arameters" Her*a medicines may !ave 'reat $otentia

in t!e mana'ement of HIV-AIDS !o%ever ri'orous

researc! is required to determine safety and efficacy"

Conflictof InterestStatement

#!e aut!ors !ave no confict of interest to decare"

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herbal medicine in the management and treatment of hiv-aids - a review of clinical trials

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