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Effect of a single bout of acute exercise on plasma human

immun odefi ciency virus RNA levels

RON EN N ROUB EN OF F ,1,2,3 PA UL R. S K OL N I K ,2 ABBY SHEVITZ,1 LAU RA S NYDMAN,1

ALICIA WANG,2 SUZANNE MELANSON,2 AN D S H ERWOOD G ORB A CH 1,2

1D ep a r t m en t of C om m u n i t y H ea l t h a n d 2Tupper Resear ch I nstit ut e, Departm ent of M edi cine,

Tufts U ni ver sit y School of M edi cin e, B oston 02111; and 3Jean Mayer United States

Department of Agriculture Human Nutri t ion Research Center on Aging at Tufts Universi ty,

Boston, M assachusett s 02111

Roubenoff, Ronenn, Paul R. Skolnik, Abby Shevitz,Laura Snydman, Alicia Wang, Suzanne Melanson, andSherwood Gorbach Effect of a single bout of acute exerciseon pla s ma huma n immunodefi ciency virus R NA levels . J .A p p l . P h y si o l . 86(4): 11971201, 1999.Acute exercise isknow n t o a ct iva t e t he immune s ys t em a nd t hus could lea d t oincreased human immunodeficiency virus (HIV) replication.We s ou g h t t o d e t e r m in e w h e t h er a s in g l e a c u t e b o u t ofexercise, similar to wh at people experience when sta rting ani n t en s iv e e xe r ci s e p r o gr a m , h a s a d e t r im e n t a l e ff ec t onp la s m a H I V R N A l ev el s . Tw e n t y -fi v e p a t i e n t s w i t h H I V

infection performed one 15-min bout of acute exercise. Abso-lut e neut rophil count s , s erum crea t ine phos phokina s e, a nd72-h urinary 3-methylhistidine (a marker of muscle proteinbrea kdow n) w ere mea s ured before a nd a f t er t he exercis e,along with plasma HIV RNA levels. There were increases inneutrophil counts (P 0.06), serum creatine phosphokinase(P 0. 01), a nd urina ry 3-met hylhis t idine (P 0.01) inresponse to exercise, indicat ing a mild a cute-phase r esponsew it h mus cle prot eolys is . How ever, mea n HI V R NA , w hichwa s elevated a t ba seline in 22 of the 25 subjects (mean of 4105 0.7 105 copies/ml), did not in creas e durin g th e weekaft er exercise (P 0.12). Sma ll changes in RNA were seen int he t hree s ubject s w it h init ia l ly undet ect a ble H I V R NA, butthe significance of these changes is unclear. Acute exercisedoes not have a deleterious effect on HIV replication in adults

w it h high vira l loa ds . B eca us e regula r exercis e t ra ining ha snot been shown t o activat e the a cute-phase response, the la cko f i n c re a s ed v ir a l l oa d s i n r e sp on s e t o a n a c u t e e x er ci s eintervention suggests that exercise training is safe in peoplewit h HI V infection.

i m m u n e s y s t e m ; h u m a n i m m u n od e fi c ie n cy v i ru s ; h u m a nimmunodefi ciency virus infection; a cute exercise

HU MAN I MMU NO DE FI C I E NC Y VI RU S (HIV) infection ca usesa ca t a b ol ic d i s ea s e t h a t l ea d s t o r ed u ce d p h y s ica lactivity, deconditioning, and loss of both aerobic capac-i ty an d m u scle stre n g th (10, 14) . Pat ie n ts with HI V

infection, but w ithout a cquired immunodefi ciency syn -d rom e (AI D S ) or p u lm on ary d isease , h ave a re d u ce dw orkload , lower a na erobic threshold, a nd poorer a ero-bic capacity than do age-matched controls (15). Exer-cise train in g is an at tract ive ad ju n ct to an tire tro viralt h e r a py i n r eh a b i li t a t i n g t h e e xe r ci s e c a p a ci t y a n dfu n ctio n al s tatu s o f p atie n ts with HI V in fe ctio n , an d

both aerobic and resistance training may be importanta djuncts t o the medical t reat ment of HIV infection. Tore ve rse we ak n e ss an d wastin g , i t is n e ce ssary to e m -ploy high-intensit y progressive resista nce tr a ining, wit hsubjects working a t 75%of ma ximum ca pacity (8, 13,24). With th e ad ve n t of h ig h ly act ive a n tire troviralthera py, abdominal obesity an d regiona l fat r edistribu-tion ha ve been recognized as problems a ssociat ed wit hHI V infection (16, 17). H owever, it is a lso possible th a texercise, especially high-intensity exercise, could acti-

vat e the immune system and t hus increa se HIV replica -tion, as occurs after vaccination (27). This has led toco n ce rn ab o u t th e safe ty o f s tart in g a h ig h - in te n si tyexercise progra m in pat ients wh o have been sedenta rya nd/or ill w ith opport unist ic infections.

I n h e al th y a d u lts , a s in g le acu te b ou t of e xh au stiveexercise clearly activates the immune system, causingleukocytosis, neutrophilia, and lymphopenia, with vari-ab le e f fe cts o n th e rate o f in fe ctio n with re sp irato ryviruses (3, 7, 18, 20, 22). S everal st udies ha ve found a nincreas e in ex vivo neutr ophil an d monocyt e pha gocyt iccapacity after high-intensity aerobic exercise (19, 21,23). H owever, oth er funct ional in dexes of immune cells,such as na tura l killer (NK) cell function and neutrophil

oxidative burst, are unaffected or decline (18). In addi-tion, acut e exercise induces production of the infl a mma -tory cytokines interleukin (IL)-1 and tumor necrosisfactor (TNF)-, which exert profound effects on meta-b o lic an d e n d o crin e p ath ways an d can in cre ase HI Vreplication (1, 2, 4, 9, 11, 12, 26). IL-1 has been linkedto t he induction of muscle protein tur nover, w hich is are qu isi te fo r in cre asin g m u scle m ass in re sp o n se toexercise (9). IL-1 h a s a l s o b e en d em on s t r a t e d i nm u scle af te r acu te e xe rcise an d co rre late s we ll withmicroscopic evidence of da ma ge a fter such exercise (5,6). I n con t r a s t t o t h e s it u a t i on w i t h a c u t e e xe r ci s e,p rog re ssive re sistan ce e xe rcise on an on g oin g b asisd oe s n o t ap p ear to a ct ivat e t h e im m u n e syst e m (25).

However, when a person begins a t ra ining progra m forth e fi rst t im e , h e or sh e is s tre ssin g m u scles in a wa ytha t ha s much in common wit h a cute exercise. This ha sraise d th e qu e stion of w h e th er b eg in n in g a tra in in gp rog ram cou ld b e d e le teriou s to th e h e al th of HI V-infected adult s.

O nl y on e s t ud y h a s ex a m in ed t h e eff ect of H I Vinfection on th e immune r esponse to exercise. U llum etal . (28) e xam in ed th e d i ffere n ce in th e im m u n e re -s pon s e t o a c u t e e xe rci se b et w e e n a g r ou p of e ig h thealth y subjects a nd a gr oup of eight patients w ith H IVin fe ction , m at ch ed in ag e an d g en d e r. All su b je cts

The costs of publication of this article were defrayed in part by thep a y m e n t of p a g e c h a r g es . Th e a r t ic le m u s t t h e r ef or e b e h e r e b ymarked advertisement in accordan ce with 18 U.S.C. Sect ion 1734solely to indicate this fact.

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e xe rcised on a b icycle e rg om e te r for 1 h at 75% ofmaximal oxygen uptake. The postexercise increases inneutrophils, NK cells, IL-2-stimulated NK cells, andlymphokine-activated killer cells were blunted in theH IV-seropositive gr oup compared w ith th e cont rol sub-jects. However, both groups had a comparable transientincrease in their CD4 counts during exercise. Thus ita ppea rs t ha t H IV infection can suppress feat ures of the

im m u n e re spon se to acu te e xe rcise. Th e con ve rse ,whether there is an effect of exercise on HIV infection,is n o t k n own . M ost p atie n ts s t art in g e xercise th e rap ya s p a r t of t h e ir t r e a t m e n t f or H I V s h ou l d p er f or mhigh-int ensity, but not exha ust ive, exercise. Therefore,we stu d ied th e e ffect of a s in gle b ou t of s tre n u ou se xer ci se, com pa r a b le t o t h e b eg in n in g of a h ig h -intensity training program, on plasma HIV RNA in 25a dults w ith H IV infection.

METHODS

S tu d y p o p u l a t i o n . Subject s w ere eligible for t his s t udy i ft h e y w e r e i n f e c t e d w i t h H I V a n d w e r e p a r t i c i p a n t s i n a n

ongoing, longit udina l s t udy of nut r it iona l s t a t us during H I Vinfection (Nutrit ion for Life, Tufts U niversit y School of Medi-cine). HIV infection w as d ocumented by ELI SA in a ll subjects.Weight loss or AIDS (on t he ba sis of the revised 1993 Center sfor Disease Contr ol criteria ) were not entry requirements. Alls ubject s ha d norma l rena l funct ion (s erum crea t inine 1.2mg/dl), hepa t ic funct ion (a s pa rt a t e a minot ra ns fera s e a nda la nine a minot ra ns fera s e less t ha n t w ice t he upper l imit ofnorma l, t ot a l bil irubin a nd a lka line phos pha t a s e w it hin t henorma l ra nge) a nd w ere a ble t o give informed cons ent . A llsubjects were sedentary except for two, who performed mildaerobic exercise two to th ree times per w eek. No subject wa sperforming res is t a nce t ra ining. Thirt y-one volunt eers ex-p r es s ed i n t er e st i n t h e s t u d y a n d w e r e g i v en i n for m e d -consent forms. Two subjects initially part icipat ed but did noth a v e a d e q u a t e v e n o u s a c c e s s a n d w e r e r e m o v e d f r o m t h estudy. Four others a greed to enter the study bu t did not keepa mea t -free diet (n 1) or decided not t o pa rt icipa t e a f t ert h e ir i n it i a l a g r e em e n t (n 3). The other 25 volunteerscomplet ed t he s t udy s ucces s fully, a nd da t a from t hes e s ub-je ct s a r e r e por t e d h e re . Th e s t u d y w a s a p p r ov ed b y t h eHum an I nvestigat ions Review Committ ee of Tufts U niversityand the New England Medical Center.

Assessm ent pr otocol . P a r t ici pa n t s w e r e a d m i t t ed t o t h eTuft s U nivers it y School of M edicine G enera l Clinica l R e-s ea r ch C e nt e r a t t h e N e w E n g la n d M ed ica l C e nt e r o n aMonday, 3 day s before a single bout of acute exercise, whichwas performed on Thursday morning. They were dischargedon Frida y morning a nd w ere readmitt ed the following Tues-da y for 4 a ddit iona l da ys . Subject s w ere ins t ruct ed a s t o amea t -free diet by a regis t ered diet i t ia n a nd a s ked t o begin

t h i s d i e t o n t h e F r i d a y b e f o r e t h e i r fi r s t a d m i s s i o n a n d t ocont inue i t during t he s t udy. P a rt icipa nt s kept diet a ry re-cords for 3 da ys before t he fi rs t a dmis s ion a nd during t he 4days between the first and second admission, to allow assess-ment of t heir us ua l diet a ry int a ke a nd complia nce w it h t hemea t -free diet . During t he t w o a dmis s ions , a l l mea ls w ereprovided by the General Clinical Research Center staff. Bodycomposition was assessed by dual-energy X-ray absorptiom-e t r y b y u s in g a H o log i c Q D R 2 00 0 w i t h v er s ion 5. 64As of t w a r e . G r a m s of l e a n m a s s , f a t m a s s , a n d b o n e m i n er a lwere m easured. I n a ddition, 24-h urin e collections for creati-nine a nd 3-methy lhistidine (3-MH) were obta ined during the3 days preceding the exercise session and again on d ays 5 7

a f t er t he exercis e, t o es t ima t e mus cle prot ein cont ent a ndprotein breakdown, respectively.

P la s ma HI V R NA w a s mea s ured in a res ea rch ret rovirol-ogy la boratory by using a Roche Amplicor Monitor RT-P CRa s s a y a ccording t o t he ma nufa ct urer s ins t ruct ions (R ocheM olecula r Sys t ems , Somerville, NJ ). B lood s a mples w erecollect ed in cit r ic a cid-s odium cit ra t e a nhydrous -dext ros etubes before th e exercise protocol and 2, 6, 24, a nd 168 h (1w k) a f t er t he exercis e s es s ion. P la s ma w a s s epa ra t ed w it hin30 min, frozen at 70 C, an d tha wed just before assa ying. Alls a mples from individua l s ubject s w ere ba t ched a nd a s s a yedtogether. For t he th ree subjects found t o have 400 copie s/m l,r e su l t s w e r e c h eck ed b y r e pe a t i n g t h e m e a s ur e m en t s b yusing the ultr asensitive Amplicor Monitor assa y syst em wit ha detection limit of 25 copie s/m l.

Complete blood counts a nd d ifferentia ls, creatine phospho-kinase (CPK), and routine chemistries were measured by theNew Engla nd M edica l Cent er clinica l la bora t ories by us ingcommercial assays. 3-MH was measured in the New EnglandMedical Center Amino Acid Laboratory by using a Beckman6300 amino acid analyzer (Beckman Instruments, Palo Alto,CA) (29).

Exerciseprotocol.All subjects completed th e exercise proto-col, consisting of 15 min of a 60-cm (vertical distance) step

aerobic. P ar ticipants w ere instructed to step up wit h their leftleg fi rst , then the right, and st ep down wit h their left leg fi rst ,follow ed by t he r ight , a t a ca dence of 1 s t ep/s . Thus ea chperson lifted his or her w eight 225 times a nd put it down 225t imes in 15 min. The lef t leg complet ed 225 concent ricexercis es (genera t ing force w hile s hort ening) a nd t he r ightleg completed 225 eccentric exercises (generating force whilelengthening). Even fit participants found this exercise diffi-cult . One subject required a 30-s rest period after 5 min andaga in a fter 10 min t o complete the protocol.

Statistical analysis. The ma jor out come of t he s t udy w a sthe change in viral load from baseline to after exercise. Datafor ea ch s ubject w ere plot t ed, a nd t he percent cha nge fromba s eline w a s ca lcula t ed. Da t a w ere exa mined gra phica lly a nds t a t is t ica lly for norma lit y . A na lys es of vira l loa d w ere per-

formed after logarithm base- 10 transformation by using theorigina l a ssa y r esults (sensitivit y 400 copies/ml). The percentcha nge w a s compa red w it h t he null hypot hes is of no cha ngeby using repeated-measur es ANOVA for HI V RNA levels,CP K, an d neutrophil counts. 3-MH results w ere measured bya pa ired t-test, comparing the mean 3-MH excretion for the 3day s preceding the exercise to the mean of the 3 days a fter th eexercis e. R es ult s w ere cons idered s t a t is t ica lly s ignifi ca nt i fthe result of a t wo-ta iledPv a l u e w a s 0.05.

RESULTS

Subject character isti cs. Ta b l e 1 s h ow s t h e d em o-g r a p h ic a n d l a b or a t o r y ch a r a ct e r is t i cs of t h e s t u d yp o p u latio n . T h e re we re 21 m e n an d 4 wo m e n in th e

stu d y, of wh o m 9 we re A frican -Am e rican s, 15 w e reCa u casia n s, a n d 1 w as a N at ive Am e rican . Th e ir r iskfactors for HIV infection were injection drug use in 11,h om ose xu al con ta ct in 13, an d u n k n own in 1. Th e irm e a n a g e w a s 3 8 y r . E i g h t e e n o f t h e p a t i e n t s w e r eta king zidovudine, either a lone (a t the beginning of thes t u d y ) or i n com b in a t i on w i t h l a m i vu d in e, or w e r eta king lamivudine wit h or wit hout sta vudine. Twelve oft h e p a t i en t s w e r e t a k i n g a p r ot e a s e i n hi bi t or. Tw op a t i en t s w e r e t a k i n g n o a n t i r et r ov ir a l t h e r a py a t a l l .No patients were taking glucocorticoids, anabolic ste-roid s, or g rowt h h o rm on e . Pa t ie n ts w e re n ot ad m itt e d

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within 1 mo of an acute infection or a change in theirantiretroviral regimen.

Developm ent of an acute-phase response to exer cise.Th e a c u t e e xer ci se w a s f ol low e d b y a n i n cr e a s e i ncircu lat in g n e u tro p h il co u n ts. T h e re was a tre n d to -ward an in cre ase in n e u tro p h ils af te r e xe rcise (P 0.06, repea ted-measur es ANOVA), especially a t 2 haf te r b ase l in e (P 0.01 post hoc pa irwise a na lysis vs.ba seline) (Fig. 1A ). There wa s a significa nt increase inC P K ov er b a s el in e (P 0.01, repeated-mea suresANOVA), wit h a sig nifi ca nt r ise by 6 h postexercise (P0.05, p ost h oc p airwise a n alysis), a n d a fal l b ack t ob ase l in e b y 1 w k (P 0.05 vs. 24 h postexercise, posth oc p a i r w is e a n a l y si s) (F i g. 1B). Sevent y-tw o-hoururinary excretion of 3-MH, a marker of muscle proteintu rn o ve r, was sig n ifi can tly h ig h e r af te r th e e xe rcise

compar ed wiht a t baseline (Fig. 2,P 0.01), indicat ingincreased muscle protein breakdown in response to theexercise intervent ion.

Effect of exercise on vir al load. M ea n H I V R N Aconcentr a tion in plasma wa s 4.1 105 copies /m l befor et h e e x er ci se t r e a t m e n t b eg a n , a n d t h e m e d ia n w a s3.9 105 copies/ml. In cont ra st to th e increase in a cutep h ase m a rk ers see n w ith th e e xe rcise in te rven tion ,th e re was n o sig n ifi can t in cre ase in circu lat in g viralRNAafter exercise (Fig. 3, P 0.12). In fa ct, there w a sa statistically, but not biologically, significant reductionin HI V RNA2 h a fter t he exercise (Fig. 3,P 0.01, posthoc analysis). The response to exercise did not differsig n ifi can tly b etw e en p atie n ts t ak in g p ro tease in h ib i-

to rs a n d t h ose n ot ta k in g th e se m ed icat ion s (d ata n otsh own ). N o p atie n t h a d a n in crease in H I V RN A th a te xce ed ed 0. 3 l og d u r in g t h e s t u d y, a n d n o p a t i en trequired a cha nge in ant iretrovira l therapy wit hin 2 wkof completing th e stud y.

Only th ree of the volunteers ha d undetecta ble (400copies/ml) levels of H IV RNA a t study entry. Theirre su lts we re ch e ck ed b y re pe atin g th e m e asu re m en tsby using a more sensitive RT-P CR a ssa y w ith a detec-tion limit of 25 copies/ml. As sh own in Ta ble 2, t herewe re sm all ch an g e s in H I V RN A con ce n trat ion a t 1 wkafter exercise in two of the patients, and at 24 h in the

th ird. The biologica l signifi cance of these chan ges is notclear.

DISCUSSION

The purpose of this st udy w a s t o exam ine whether amoderately intense bout of exercise, similar in inten-s it y t o a fi r s t -t i m e t r a i n in g s es s ion , w o ul d i n cr ea s e

ci r cu la t i n g H I V R N A in p a t i en t s i n fect e d w i t h t h i svirus. Although the potential benefits of exercise forpeople w ith H IV ar e clear, including improved strengt h,fu n ction al s t at u s, lean b od y m a ss, an d an a b olic s tat e ,an increase in circulating HIV could be a major nega-tive effect of exercise. There is t heoretical r eas on to beconcerned a bout this, beca use a cute exercise clea rlya ctivat es the immune syst em, increasing production of

Ta ble 1. Basel i ne demographic, cl i ni cal, andlaborat ory featu r es of the 25 stud y patients

Pa r a m e t e r

Age, y r 39.3 (29 55)G en der, M:F 21:4Weigh t , kg 77.313.1L ea n body m a ss, kg 56.38.0

H em oglobin, g/l 13.81.4S er um cr ea t in in e, m g/dl 0.870.18Aspa rt at e a min ot ra nsfer a se, U /l 3482C r e a t in e p ho sp h ok in a s e (b a s el in e), U /l 1 0379Neut rophil count (baselin e), no./mm 3 2,459974CD 4 count, no./mm 3 335 (10744)H IV RN A, copies/ml

MeanS D 4.11050.7 105

Media n 3.9105 (252.2106)

Values are means S D w it h r a n g e in p a r e n t h e s e s . M , m a le ; F ,female; HIV, human immunodeficiency virus.

Fig. 1. Acute-phase response to exercise. A : circulat ing a bsoluteneutr ophil counts/mm 3. B: c r ea t in e p h os p h ok in a s e (CP K ) lev e ls(mU /ml). Time points (T) ar e ba seline a nd 2, 6, 24, a nd 168 h (1 wk)after 15 min of acute exercise, expressed as a percentage of baselinevalue for each subject. Mean neut rophil count for each follow-up timeis s h ow n b e low g r a p h . Er r or b a r s , S E. P a ir w is e c om p a r is on t e s t sdifference for each point compared w ith it s immedia te predecessor.

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several inflammatory cytokines including IL-1, IL-6,and TNF-, which, in turn , hav e been show n to upregu-late HI V re plicat ion in vi tro (3, 7 , 18, 20, 22). A ne xam p le o f im m u n e activat io n , vaccin atio n , was re -cently shown to cause a transient increase in circulat-in g HI V (27). We th e re fore d e sig n ed th is s tu d y toexamine short-term viral load kinetics in response toone bout of moderately heavy exercise. In our previousstudies of the immune response t o regular progressiveresistance training, we found no immune activation ofan y sort in h e al th y volu n tee rs an d p at ien ts w ith a u to -

im m u n e d isease (rh e u m ato id art h ri t is) af te r 12 wk ofbiweekly training (25). Thus the chief concern in rela-t i o n t o i n c r e a s i n g H I V r e p l i c a t i o n i s a t t h e s t a r t o fex er ci se t r a i n i n g, b eca u s e t h e fi r s t t i m e u n t r a i n edvolu n tee rs d o re g u lar e xe rcise, th e y are in e sse n ceperformin g a bout of acut e exercise.

The exercise intervention we used did activate theacute-phase response mildly, with increases in neutro-phil counts, CP K, an d 3-MH, indica ting th a t dema rgin-ation of circulating neutrophils and mild muscle injuryd id occu r. Th e e xe rcise in te rve n tion re qu ire d e ach

subject to lif t a nd put down his or her body w eight 225tim e s in 15 m in . Ob se rvatio n o f th e stu d y su b je ctscon fi r m ed t h a t t h ey w e re w or ki ng h a r d d u ri ng t h eex er ci se , w i t h ob vi ou s t a ch y ca r d i a , t a c h y pn ea , a n ddiaphoresis evident in a ll of them. Nevertheless, t herew a s n o i n cr ea s e i n H I V R N A du r in g a n d a f t er t h isexercise bout. This exercise wa s prima rily one of musclee n d ura n ce, b u t b ecau se su b je cts h ad to lo we r t h e irbody w eight slowly, there wa s a considerable eccentr iccomponent to the int ervention a s well. Thus t he resultsof th e p resen t s tu d y sh ou ld b e a p plicab le to s tre n g thtraining as well as endurance training. However, thesere sults p rob ab ly sh ou ld n ot b e g e n era l iz ed to lon g -duration or very-high-intensity exercise, such as pro-

lo n g e d ru n n in g , a s t im u lu s th at h as b e e n stu d ie d b yoth e rs as an e xam p le of e xe rcise-in d u ce d im m u n eactivatio n (19). G ive n th e se d e n tary h ab its an d p o o rphysical fitness of our subjects, we were concerned thatusing such an intensive protocol could lead to injury oruntowa rd immune effects.

We conclude that starting an exercise program at am o d e rate le ve l o f in te n si ty is n o t asso ciate d with anincrease in HI V load. I t sh ould be noted th at the mea nH I V l o a d o f o u r p a r t i c i p a n t s w a s r e l a t i v e l y h i g h a tbaseline, and it is possible that large increases in HIVRNA were sim ply not seen because of a ceiling effectin HIV replication. No such ceiling effect was seen interms of the HIV RNA a ssa y itself . Alterna tively, sma ll

chan ges in HIV RNA w ould be more difficult t o see witha h ig h b a s el in e R N A lev el t h a n i n t h e s et t i ng ofpreviously undetecta ble levels. B eca use th e th ree sub-je ct s w i t h b a s el in e u n d et e ct a b l e H I V R N A s h ow e dsm all t ran sie n t in cre ase s in viral lo ad , t h e e ffect ofacute exercise on HIV RNA in such patients deservesf ur t h e r s t u d y. I t i s p os s ib le t h a t p a t i en t s w i t h l ow baseline circulat ing H IV could be more susceptible toa n increase a fter exercise tha n were those wh o a lreadyhave elevated rates of HIV replication. Nevertheless,given t he ma ny benefi ts of exercise for t his populat ion,our results suggest that programs of regular exercise,

Fig. 2. Seven ty -tw o-hour urin a ry 3-met hylh istid ine excret ion (mol/gcreat inine) for 3 da ys before exercise and 3 days after acute exercises e ss ion . M u s cle fi b r i l l a r p r ot e in t u r n ove r in cr e a s ed s ig n ifi c a n t lyaft er exercise (P 0.01).

Ta ble 2. E ffect of acut e exer cise on plasma H I V RN A(copies/ ml ) in the 3 subjects wh o had u nd etectable

levels at baseline

Age, yr/G ender B a seline 2 h 6 h 24 h 168 h

47 F 25 25 25 25 7251 M 116 84 144 180 114

38 M 25 25 25 25 218

Fig. 3. Serum huma n immunodeficienty virus (HIV) RNA measuredby RT-P CR at baseline a nd 2, 6, 24, an d 168 h (1 wk) after 15 min ofacute exercise, expressed as a percentage of baseline value for eachsubject. Mea n log concentra tion for each follow-up time is a lso shown(bottom). Er r or b a r s , S E . Th e r e w a s n o s ig n ifi c a n t c h a n g e in R N Aafter exercise (P 0.12, repeated-measures ANOVA), although astat ist ically s ignifi cant , but biologically unimporta nt , decline in RNAwa s seen 2 h aft er exercise compar ed with ba seline (P 0.01, post hocpairwise a nalysis).

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aim e d a t in cre asin g stre n g th a n d m u scle m a ss, re d u c-i n g f a t m a s s , a n d i m p r ov in g f u n ct i on a l s t a t u s i n p a -tients wit h H IV infection, should be implemented w ith-out excessive concern a bout the r isk of activat ing H IVreplication with moderate exercise.

The aut hors tha nk J oan ONeil and other members of the GeneralClinical Research Center s taff a t the New England Medical Centerf or a s s is t a n ce w it h t h is s t u d y ; J a m e s R a y m on d a n d t h e s t a f f of t h e

Nutrition for Life project for assistance with recruitment; LeslieAbadfor superb technical assist an ce; Dr. Mar y Ampola for the 3-methy lhis-t idine measurements; a nd t he volunteers for their blood, sweat , toil ,and occasional t ears .

Address for reprint requests and other correspondence: R. Roube-noff, Nutrition, Exercise Physiology and Sarcopenia Laboratory, J eanMa yer U SD A HNR CA, Tufts U niv., 711 Wash ington S t., B oston, MA02111 (E-mail roubenoff@hnrc.tufts.edu).

This study was supported by National Inst itutes of Health GrantDK-45734 and thr ough the G eneral Clinical Research Center fundedby D ivision of Research R esources G ra nt M01-RR-00054.

The content s of this publication do not necessarily refl ect the viewsor policies of the U. S . Dept. of Agricultur e, nor does mention of tra denames, commercial products, or organizations imply endorsement bythe United Sta tes government.

Received 30 J uly 1998; accepted in fi na l form 23 November 1998.

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