INTERNATIONAL JOURNAL OF BEHAVIORAL MEDICINE, 1(I), 90-105 Copyright �9 1994, Lawrence Erlhaum Associates, Inc.

Distress, Denial, and Low Adherence to Behavioral Interventions Predict Faster Disease Progression in Gay

Men Infected With Human Immunodeficiency Virus

Gall Ironson, Andrea Friedman, Nancy Klimas, Michael Antoni, Mary Ann Fletcher, Arthur LaPerriere,

John Simoneau, and Nell Schneiderman

This study examined psychological predictors of 2-year disease progression in gay m e n af te r f i nd i ng out their h u m a n immunodef ic iency vi rus (HIV) scrostattm. Psychological and immune status of asymptomatic gay men who did not know their HIV serostatus was monitored during the 5 weeks before and after serostatus notif ication. The men were randomly assigned to an exercise, cogni t ive-behaviora l s t ress-management intervention, or control group. At 2- year fol low-up for the 23 men who turned out to be seropositive, 9 had devel- oped symptoms, including 5 with acquired immune deficiency s y n d r o m e - - 4 of whom died. Distress at diagnosis, denial (5 weeks postdiagnosis minus pre- d iagnosis) , and low adherence during interventions were signiHcant predictors of 2-year disease progression. Denial and adherence remained signif icant pre- dictors of disease progression even after controll ing for CD4 number at entry. Fur thermore, change in denial was significantly correlated with immune status 1 year later; 1-year immune status was significantly correlated with 2-year

Gall [ronson, Andrea Friedman, Nancy Klimas, Michael Antoni, Mary Ann Fletcher, Arthur )

and Medicine, Univeraity of Miami, Miami and Co~'al Gables, FI., USA, and the Miami Veterans Administration Medical Center, Miami, FL, USA.

This research was supported by National Institute of Menial Health Grants PS0-MH4355, PO 1-M]-149548, and T'32-MHI8917.

We dedicate this article to the memory of John Simoneau, who was enormously helpful in emsuring that the follow-up was done and who performed many of the physicals before his untimely death in January 1992 due to AIDS.

We also ate iadebtted to Lane Baggett, Sharon August, and Francisco ArevaJo, who contrib uted substantially to the conduct of this project.

Correspqandence concerning this article should be addressed to Michael .A.Jatom, Department of Psychology, University of Miami, EO. Box 248185, Coral Gables, FL 331">4-2070.

PREDICTORS OF HIV PROGRESSION 91

disease progression. The present study therefore demonstrates significant rela- tions between psychological variables on the one hand and both immune mea- sures and IIIV-1 disease progression on the other. We conclude that distress, denial, and low protocol compliance predict subsequent disease progression.

Key words: acquired immune deficiency syndrome (AIDS), human im- munodefieieney virus (HIV), disease progression, distress, immunity, denial, coping, adherence, health

Despite the severity of the acquired immune deficiency syndrome (AIDS) epidemic, only a few studies have examined relations among psychosocial variables, immune status, and health-related declines. The notion that psy- chosocial variables such as distress might be related to immune variables receives support primarily from studies of immunologic impairment in healthy individuals exposed to stressors such as medical schoo~ examina- tions and marital discord and divorce (Kieeolt-Glaser et al., 1987; Kiecolt- Glaser, Garner, Speicher, Penn, & Glaser, 1984; Kiecolt-Glaser & Giaser, 1991; Kiecolt-Glaser et al., 1986; Kiecolt-Glaser et at., 1988); for health-re- lated outcomes, the development of colds (S. Cohen, Tyrrell, & Smith, 1991) and the success of the hepatitis B vaccine in stimulating antibody formation have similarly been related to relatively commonplace psychosocial stressors (Glaser, Kiecolt-Glaser, Bonncau, Malarkey, & Hughes, 1992).

Only a few published studies have prospectively related psychosoeial variables to health and immunity in the context of human immunodeficiency virus-Type 1 (HIV-I) infection, and these have produced predominantly negative results. Perry, Fishman, Jacobsberg, and Frances (1992), for exam- ple, found no relation between CD4 cell count and 22 psychosocial variable measures (an exception was hopelessness, which related to lower CD4 counts). Perry et al. did note, however, that greater emotional distress was predictive of the severity of physical symptoms. Rabkin et el. (1991) also found no relation among depressive disorders, psychiatric distress, psy- ehosocial stressors, and CD4 and T-suppressor/cytotoxic (CDS) cell changes over a 6-month period, but they did find a "suggestive pattern of association" between depression and a greater number of HIV-l-related symptoms. Most recently, Burack, Stall, Barrett, and Coates (1992) reported that depressed HIV-positive gay men showed a faster decline in CD4 cell counts over a subsequent 6-year period when compared to their nondepressed counter- parts. However, depression did not predict accelerated disease progression over this period. Thus, the evidence appears to be inconclusive for the relation among psychosoeial factors, immune markers, and disease progres- sion in HIV-infeeted populations.

Possible reasons for the negative findings relating psychological vari- ables to immune markers and disease progression--if indeed positive rela- tions do exist--include (a) heterogeneity in the source of infection and disease stage of subjects at the point of study entry (baseline), (b) heteroge-

9 2 A;~

nelly of study subjecls in terms of gender, ethnicity, and drug abuse, (c) age, (d) too limited a selection of immune markers, and (e) a failure to assess individual differences in transactional variables such as coping strategies used to deal with specific stressors. Because the course of HIV infcclion may be less affected by psychosocial and behavioral factors at later stages of disease progression, samples made up of subjects differing in source or stage of infection, age, gender, or ethnieity may produce extraneous sources of variance, thus making it difficult to detect the influence of these factors. By recruiting only healthy asymplomatie homosexual men in the present study, we were able to minimize this problem. Whereas the sludies that failed to find differences between psyehosocial and immune markers restricted them- selves to examination of CD4 and/or CD8 number, the present study also examined a marker of CD4 eelI function--the in vitro lymphocyte response to phyto-hemagglutinin (PHA)--ihat has previously been found to be sensi- tive to psychological variables (lronson et al., 1990), associated with HIV disease progression (Page el al., 1990), and able to differentiate disease p r o g r e s s o r s f rom n o n p r o g r e s s o r s in HIV-1 seroposilive s u b j e c | s (Schellekens, Rods, De Wolf, Lartg, & Miedema, 1990).

As already mentioned, prior studies have failed to evaluate the role that transactional factors played as potential psyehosocial predictors of health outcomes. Two such transactional factors receiving attention as mediators of health oulcomes among stressed individuals dealing with life-threatening conditions are denial and active-involvement coping strategies. For instance, although active behavioral strategies have been associated with better ad- justment in individuals dealing with AIDS (Namir, Wolcott, Fawzy, & At- umbaugh, 1987) and other chronic illnesses such as cancer (Fawzy et al., 1990: Feltcn, Revenson, & Hinrichsen, I984), denial and avoidance coping appear to predict poorer adjustment. Additionally, our previous work sug- gests that denial and avoidance strategies predict greater impairments in immune status among HIV-infccted gay men (Antoni, Goodkin, el al., 1991). However, no work to dale has related active coping and denial to the clinical progression of HIV infection prospectively in this population.

In addition, although there are a few prospective studies examining the relation between psychosocial factors and disease progression, no studies have obtained such data from asymptomalic individuals during the process of finding out their HIV diagnosis. Such a study would permit one to use distress al the time of diagnosis and coping obtained prospectively before and after the diagnosis as predictors of later disease progression. Serecting a sample of men who were asymptomatic and who did not know their HIV status (or T-cell counts) helps to disentangle the problem in prospective studies of not knowing which is causal in the constellation of having symp- toms, depression, and CD4 change. Our work, whose short-term results have been reported previously (Antoni, Baggett, el al., 1991; Estcrling el al., 1992; lronson et al., 1990; LaPerriere et al., 1990), look place in the context of behavioral stress management and exercise interventions designed to

PREDICTORS OF HIM PROGRESSION 93

buffer the effect of notification of HIV status. It is important to note that no studies have been published relating intervention-associated changes in psy- chological status to future health status.

The present study used changes in coping and distress at the time of diagnosis to predict the development of Centers for Disease Control (CDC, t987) Stage 4a symptoms (formerly AIDS-related complex; ARC) and "frank AIDS" (CDC Stages 4b to 4e) among initially symptom-free HIV-1 seroposilivc gay men. Because we also collected extensive information on the men's attendance at treatment sessions and home practice of stress-man- agement techniques, this design also made possible the measurement of a third predictor not present in the current literature--namely, treatment ad- herence, which includes attendance, relaxation home practice, and comple- tion of homework assignments. We viewed treatment adherence as an excellent way to operationalize active coping strategies. Thus, the purpose of this article is to examine prospectively the rote of these three previously unexplored psychosocial variables evidenced during the course of behav- ioral interventions in the prediction of HIV-related disease progression.

METHOD

Subiects

Eighty-one healthy gay mcn agreed to participate in a study of stress, psy- chosocial factors, and immune functioning during the course of which they would be learning their HIV serostalus. Subjects were all asymptomatie at the time of entry into the study. A complete physical examination by a physician or physician's assistant, along with an aerobic fitness evaluation and mcdicai/psychosocial history, was conducted before entrance into the study. Subjects were excluded if they displayed any of the following: having been previously tested for HIV antibody; diagnosis of AIDS or other H1V-re- lated diseases; herpes zoster or unexplained weight loss of more than 15 Ib (or 10%) within the previous 3 months; mucocutaneous oral candidiasis; lymphadenopathy other than inguinal or anterior cervical; diarrhea, night sweats, or fever of unexplained origin; or producing an estimated VO2max greater than 53 ml/kg/min if 18 to 29 years old or 49 ml/kglmin if 30 to 39 years old. Subjects were also excluded for any of the following behaviors: current drug or ethanol abuse; use of anabolic steroids; regular use of antihistamines; or ongoing participation in a regular aerobic exercise, relax- ation, meditation, or psychotherapy program. Of the 81 men recruited, 30 were found to be HIV-1 antibody posilive, and 51 were found to be HIV negative. Of the 30 positives, 27 completed at least one data-collection point after finding out their HIV status. Twenty-three of the 27 men were exam- ined for disease progression 2 years after receiving their HIV diagnosis.

Sociodemographic characteristics of the sample have been described else- where (lronson el al, 1990).

94 :: ~ONSOX :;;1:

Design

At point of entry, after the baseline assessment and blood draw were com- pleted, all subjects were randomly assigned to either a cognitive-behavioral stress-management (CBSM) group, an aerobic exercise (AE) training pro- gram, or an assessment-only control condition. The CBSM and AE interven- tions were conducted in groups of 4 to 6 men for 135 rain/week (across either two or three weekly sessions). Five weeks after entry, blood was drawn from subjects in order to determine their HIV-1 antibody status. The results of their anlibody test were disclosed to them by a licensed clinical social worker within 72 hr. Subjects remained in the first phase of the study (intervention or control) for another 5 weeks postdiagnosis. They were then followed for the assessment of disease progression 2 years after entry to the study. Details of the interventions and measures (immune and psyehosocial) were described in Esterling et al. (1992). Wc limit the description here to measures used in the analysis or longitudinal data.

Psychosocial Measures

State-Trait Anxiety Inventory (STAI). The State version of the STAI (Spieibcrger, Gorsuch, & Lushene, I970) was used as the index of anxiety. This 20-item self-report instrument is designed to measure the anxiety level of the respondent at the time of administration. It has demonstrated reliabil- ity (internal consistency a s = .92 to .94) and validity (increases under conditions of experimentally induced stressors; Spielberger et al., 1970). Previously, we have shown this measure to be quite sensitive to increased anxiety at the day of notification of a diagnosis of HIV seropositivity (Iron- son et al., 1990). We used the STAI score measured at entry to the study and at the point of diagnosis as the anxiety measure in the present study.

Profile of Mood States (POMS). The POMS (McNair, Lorr, & Droppleman, 1981) is a 65-item self-report inventory with several subseales tapping various mood states (anxiety depression, anger, vigor, fatigue, con- Fusion) and generating a Total Mood Disturbance (TMD) score. The POMS is particularly suited to assessing changes in distress, with a l -week time frame embedded in the directions ("How have you been feeling during the past week?"). The lime points used in this study were entry In the study and 1 week after notification.

Impact of Events Scale tIES). The ]ES (Horowitz, Wilner, & AI- varez, 1979) is a 15-item self-report measure designed to tap psychological responses In Iraumatic life cvenls. We have previously found the IES to be quite sensitive for gay men discovering their H1V seropositivity (lronson et

PREDICTORS OF HIV PROGRESSION 95

al., 1990). The IES yields a Total Impact score and two subscaie scores. The Intrusion subscale measures intrusively experienced thoughts, images, feel- ings, and dreams, whereas the Avoidance subscale measures avoidance of certain ideas, feelings, and situations. Reliability (test-retest rs = .79 to .89; internal consistency ct coefficients = .78 to .82) has been established for both subscales. Only the Intrusion subscale was used in constructing a distress composite (see next section) because the Avoidance subscale was not signif- icantly correlated with any of the other distress measures (STAI, POMS) postnotification in our data. The time points used in this study were entry |o the study and 1 week after notification.

Distress composite. Because the sample size was small, and because the POMS-TMD, STALl, and IES Intrusion subscale were correlated, we investigated the possibility of combining them into a composite score repre- senting distress. A principal-components factor analysis of the three scores at the distress time point (postnotification) yielded one eigenvaluc greater than 1 (=1.97) with alI three scales loading greater than .75 on the first factor in the unrotated factor matrix. A similar factor analysis of the three scores at entry to the study yielded one eigenvalue greater than 1 (+1.91), with all three scales loading greater than .61 on the first factor in the unrotated factor matrix. As a result, the three scales (POMS-TMD, STAI, and IES Intrusion subscale) were each changed to z scores (to equalize variances) and then summed to form a composite score representing distress at the two time points (entry to the study and postnotification). Distress increase was calcu- lated by the distress value postnotification minus the distress value at entry to the study.

Denial coping. Denial Coping is a four-item subscale of the COPE, a self-report measure tapping several different types of coping used to deal with stressful situations (Carver, Scheier, & Weintraub, 1989). We focused on denial because we felt it might be the most maladaptivr coping style. We defined denial as an attempt to deny the reality of the stressful event. Items on the Denial Coping subscale are "I refuse to believe that it has happened," "I pretend that it hasn't really happened," "I act as though it hasn' t ever happencd," and "I say to myself this isn' t real." At entry to the study, subjects responded to the COPE (prediagnosis) in terms of how they were dealing with the prospect of finding out their HIV status 5 weeks later. Five weeks a f t e r d iagnos i s of HIV status, sub jec t s f i l led out the COPE (postdiagnosis) in terms of how they were dealing with having found out their HIV status and with the threat of AIDS in their life. Denial increase was calculated by the denim value postnotifieation minus the denial value at entry to the study.

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Treatment adherence. Adherence was measured for the subset of subjects in the intervention groups (n = 9 in AE, n = 9 in CBSM) first by a t tendancerpercentage of meetings atlended of 30 possible for the AE group (3 per week) and of 20 possible for the CBSM group (2 per week). Adherence was also measured within the CBSM group by frequency of relaxation practice reported by subjects. Each week, subjects recorded relax- ation practice sessions alone at home on a daily basis on a set of cards that they brought to the CBSM meetings. Recorded practice was averaged over the 10-week period to arrive at the relaxation frequency measure. Homework assignments provided a third measure of adherence--fil l ing out daily self- monitoring sheets describing stressfui events, emotions, automatic thoughts, and so forth.

Control Measures

Polenlial immunomodulatory confounds such as nutritional status (albumin), sleep, alcohol use (gamma glutamyl transpeptidase, GGTP), physical fitness, high-risk sexual activity, and stressful life events-- the Life Experience Survey (LES; Sarason, Johnson, & Siegel, 1978)--were assessed at baseline. Prior history of sexually transmitted diseases (STDs)--history of gonorrhea, syphilis, and genital herpes--was also obtained at entry to the study, as this factor has been identified as a potential co-factor for HtV disease progres- sion (Keel et al., 1990).

Immune Measures

The number of CD4 cells was measured at entry to the study as previously described (Fletcher et al., 1991) and was included in the analysis as a covariate, because it has been used as a marker of disease progression in HIV speetrum disease (Fahey et al., 1990). The proliferative response of lympho- cytes in peripheral blood to PHA was measured as described by Fletcher, Klimas, Morgan, and Gjerset (1992).

Disease Progression

Disease progression was ascertained at 2-year follow-up by physical exami- nation done by a physician or physician's assistant (John Simoneau, until shortly before his death in January 1992). Subjects were classified as having developed AIDS if they met the CDC (1987) case definition, had had an opportunistic infection (i.e., pneumocystis, eryptoeoccus, disseminated cy. tomegalovirus, or toxoplasmosis), cerebral lymphoma, Kaposi's sarcoma, or

PREDICTORS OF l ttV PROGRESSION ~7

AIDS dementia complex. Subjects were ctassified as symptomatic if they met ARC (CDC Stage 4a) cr i ter ia--night sweats or fevers (greater than 101.5 *F) of unknown origin; weight loss of more than 15 lb (or 10%) within a 3-month period; fatigue; diarrhea for 3 months; lymphadenopathy other than inguinal or anterior cervical; and oral thrush, lcukoplakia, shingles (herpes zoster), or easy bruising (with fewer than 120,0(}0 platelets). Sub- jects were classified as asymptomatic at 2-year follow-up if they had none of the symptoms of ARC (CDC Stage 4a) i3r AIDS (CDC Stages 4b to 4e), as noted earlier.

RESULTS

At 2-year follow-up, 5 of 23 men had developed AIDS (4 of these died), and 9 had developed symptoms (the 5 with AIDS plus 1 with thrush and fevers, 1 with leukoplakia, 1 with thrush, and 1 with hairy leukoplakia and shin- gles). Fourteen men remained symptom free.

Table I presents the correlations of the psychological variables (a) with symptoms, which includes ARC (CDC Stage 4a) symptoms or AIDS or death (coded 0 = asymptomatie, I = symptomatic) and (b) disease progression to AIDS (coded 0 = asymptomatie or CDC Stage 4a symptoms, 1 = AIDS or death at 2-year follow-up). Both zero-order correlations of the psychological variables with disease progression and partial correlations of the psycholog- ical variables with disease progression---controlling for CD4 number at entry to the s tudy- -were performed in order to control for subclinical differ- ences between subjects in the HIV spectrum disease at entry to the study, even though all subjecls were asymptomalie.

As can be seen in Table 1, distress upon diagnosis, distress increase (from entry to the study 5 weeks before to 72 hr to 1 week postdiagnosis), and

TABLE 1 Denial, Distress at Diagnosis, and Treatment Adherence Predict Disease

Progression

2-Year Disease Progressiona

Distress at diagnosis .5 I* .39 ..... 16 ,Ol Distress increase .59* .4t .39 .20 Denial increase ,58" .58" ,52' .52" Adherence/participatiort -.35 - . 18 .63" --.54"

"pr columns present partial corre~,atiorts o~ the psycholog~ca| variables and disease progres- sion controlling for CD4 number at entry to study. Respective Fs for the: test Of pmlia[ rs are as follows: disease progression to symptoms = 2.32, 2.60, 7.76, and 0.44; disease progression to AIDS/death = ns, 0.52, 5.53, and 5.24.

98 ~RO

denial increase (from 5 weeks prediagnosis to 5 weeks postdiagnosis) were significantly and positively correlated with disease progression to symp- toms. The relation between denial increase and symptoms was maintained even after controlling for CD4 number at entry into the study. Whereas the relation between distress and symptoms did not remain significant after controlling for CD4 at entry to the study, the partial correlation suggests a trend in the expected direction, the significance of which was limited by the small sample size. Although attendance was not significantly correlated with disease progression to symptoms, the trend was in the expected direction, with those subjects who attended more of the intervention sessions being more likely to be symptom free at 2-year follow-up.

The significant predictors of disease progression to AIDS were increase in denial (from 5 weeks prediagnosis to 5 weeks postdiagnosis) and attendance. These relations were maintained even after controlling for CD4 number at entry to the study. In addition to attendance, within the CBSM group there were two other measures of adherence---relaxation practice and homework. These were both highly and significantly related to disease progression to AIDS (r = -.71, p < .05 for relaxation practice; r = -.76, p < .05 for homework) despite the small sample size in this group (n = 9). It is interesting to note that distress upon diagnosis was not related to development of AIDS.

Descriptive statistics for the three groups are presented in Table 2. As can be seen, higher distress on receiving a diagnosis of seropositivity, higher increasc in distress from 5 weeks prediagnosis to 5 weeks postdiagnosis, and higher increase in denial from 5 weeks prediagnosis to 5 weeks postdiagno- sis were associated with a greater likelihood of having symptoms at 2-year fo l low-up . In addi t ion, g rea te r increases in denial (pred iagnos is to postdiagnosis) and lower adherence (attendance, relaxation frequency, and homework) were both associated with a greater likelihood of disease pro- gression to AIDS.

There is some evidence that denial as a coping strategy is correlated with maladaplive coping strategies such as mental disengagement and/or behav-

TABLE 2 Means and Standard Deviations for Predictors During the First 10 Weeks of

Study

2- Year 0l~tt'o~ne

No S.vrnptoms Symptoms AIDS

Predictor M SD M SD M SD

CD4 number a( entry (cells/ram ~) 892 332 505 278 342 267 Distress Mter diagnosis ~ 11 t .8 52.3 169.6 46.5 152.5 67,2 Distress increase" 16.6 75.0 I17.2 27,5 127.0 48,1 Denial increase ,4 2,4 2.9 2.2 3.5 2.5 Adherenee/atlendanee (percentage) 89.2 l 1.8 77.1 20.0 69 17.5

a .

t l smg raw sc.nres.

PRF, DICTORS OF |tiV PROGRESSION 0 9

total disengagement and is predictive of poorer adjustment among breast cancer patients dealing with mastectomy (Carver et al., 1989). In our current sample, change in denial was significantly correlated with change in behavioral disengagement (r = .48, p < .05) but not mental disengagement (r = .17, ns). Furthermore, subjects who remained asymptomatie had a significantly greater decrease in behavioral disengagement over the 10 weeks prediagnosis to postdiagnosis than those who developed symptoms at 2-year follow-up (mean change = 3.1 for asymptomatics; 1.0 for symptomaties; t = 2.08, p = .05), and change in behavioral disengagement (entry to 5 weeks postdiagnosis) was significantly correlated with disease progression to AIDS (r = .61, p < .01).

The greatest potential confound was CD4 number at entry to the study. Because it was highly correlated with the dependent variables of interest (r = .53, p < .05 with disease progression to symptoms; r = .59, p < .05 with disease progression to AIDS) and is known to be a marker for disease progression itself, we handled this by making CD4 counts at study entry a covariatc and calculating partial correlations between the psychological variables and disease progression while controlling for CD4 number at entry to the study.

Another important potential confound in a longitudinal study of this nature is the intervention group condition (AE, CBSM, or control group). In order to determine whether there was an effect of intervention condition on disease progression, we used a multiple-regression analysis to predict dis- case progression by first entering baseline CD4 number and then two dummy-coded variables representing lhc control and the two intervention groups. The dummy variables did not add significantly (beyond CD4 counts) to the prediction (F < 1 in all cases) of disease progression to either syrup- Iotas or AIDS/death. This is equivalent to a nonsignificant analysis of covar- lance controlling for CD4 number and suggests that the interventions per se were not associated with belier health at 2-year follow-up.

Other potential immunomodulatory confounds including albumin, GGTP, physical fitness, high-risk sexual activity frequency, and sleep did not show significant differences between those who progressed and those who did not progress. The same was true for negative life events and history of STDs, although there were nonsignificant (p <. 10) trends in these var iables- - those who progressed were more likely to relate a history of STDs (STD M = 1.5, SD = .7), whereas those who did not progress had an STD M of .8 (SD = 1.1). Those who progressed also had more negative life events (LES M = 4.5, SD = 3.6) than those who did not progress (LES M -~ 2.7, SD = 2.3). The STD and LES variables need to be studied with a larger sample.

Last, we wanted to investigate whether the psychological predictors and disease progression would be related to immune measures taken at an inter- mediate time point (1-year follow-up). We examined and found that change in denial was significantly correlated with 1-year immune status. Thus, increase in denial correlated - .69 with CD4 cell number at 1-year follow-up. (Partial r controlling for CD4 cell number at entry to the study was - .53.)

100 [RONSON ET AI.

Similarly, increase in denial correlated - .68 with lymphocyte response to PHA stimulation at 1-year follow-up. (Partial r controlling for CD4 cell number at entry was -.49; partial r controlling for lymphocyte response to PHA at entry to the study was - .490 In turn, l -year immune status was significantly correlated with 2-year disease progression (CD4 with AIDS, - .73; CD4 with any symptoms, - .58; PHA with AIDS, -.49; PHA with any symptoms, - .62).

DISCUSSION

The strongest and most consistent psychological predictor of deterioration of immune status and disease progression in our HIV-positive gay men appears to be the use of denial to deal with a seropositive diagnosis. Denial is defined as believing and acting as if the diagnosis of HIV seropositivity has not been made. By what vehicle might denial be related to disease progression? Likely candidates worthy of further study include a lack of doing things necessary to keep oneself healthy, such as not keeping physician appoint- ments, failing to obtain updated information about AIDS treatments, and not adhering to medication regimens (e.g., antiretrovirals such as a zidovudine, AZT). As noted, there is some evidence that denial as a coping strategy is correlated with maladaptive coping strategies such as mental disengagement and behavioral disengagement and is predictive of poorer adjustment among breast cancer patients dealing with mastectomy (Carver el al., 1989). Our data suggests that, in this sample, behavioral disengagement--a strategy reflecting helplessness rather than mental disengagement, which is more of a distraction strategy--may be lhe maladaptive coping strategy associated with denial that predicts disease progression.

Further explorations might also include determining whether denial was related to continuing unsafe sex or to using recreational drugs and a lcohol- - any of which might be a possible mechanism for its impact on disease progression. In addition, denial is generally viewed as an immature defense mechanism and thus may be correlated with poorer mental health, greater distress, and less ability to handle adverse situations well. In one study in which patients were coping with a breast cancer diagnosis, avoidance coping was a prospective predictor of high distress and low vigor during the postbiopsy and postsurgery periods (Stanlon & Snider, in press). Last, deny- ing the existence of a stressful condition may preclude one from dealing with altendant emotional reactions, thus failing to express anger, sadness, and other dysphoric emotions. We have previously related greater expression of emotions to better cell-mediated immune system control of Epstein-Barr virus (Esterling, Antoni, Kumar, & Schneiderman, 1990).

In contrast, there is evidence in the literature that denial may sometimes be useful. In post-heart attack patients, denial is associated with less distress (Gentry, Foster, & Haney, 1972), earlier resumption of work and sexual activity (Stern, Pasealc, & Ackcrman, 1977), and lower subsequent mortality

PREDICTORS OF HIV PROGRESSION 101

(Hackett, Cassem, & Wishnie, 1968). Lazarus and E Cohen (1973) found that patients who avoided thinking about the surgery they were facing fared better afterward; those ignoring the facts about what could go wrong in surgery, relying instead on faith that things would go right, recovered more quickly and had fewer complications. A few questions are raised by these disparities in the literature. First, are there characteristics of situations in which denial might be more harmful than others? These examples suggest, as Lazarus and F. Cohen noted, that the presurgieal patient has nothing to gain from vigilance, whereas, by contrast, if a diabetic denies his or her problem and fails to monitor sugar levels constantly, dire health conse- quences may ensue. Our research suggests that the patient with HIV spec- trum disease may be more like the diabet ic-- they both are dealing with a chronic disease, the course of which may be affected by behavioral factors such as adherence to treatment regime and emotional factors such as distress. A second question raised is whether there is an optimal level of denial. This optimal level might be described as being high enough so that a person is not incapacitated with overwhelming worries and anxieties and negative think- ing but not so much that the person is avoiding attending to the things that need to be done to keep as healthy as possible.

The second variable relating disease progression to symptoms was dis- tress upon diagnosis. Interestingly, distress was related to the development of symptoms but not to AIDS. Although one must rule out a reporting bias rather than a true symptom difference, in our study all symptoms were physically verifiable. Although there is a large literature relating stressful events to impaired immune function (see Kiccolt-Glaser & Glaser, 1991, for a review), both Kessler et al.'s (1991) data and our own show that negative life events per se may not be related to disease progression. In order to capture the important emotional event, one may need to ascertain distress at the critical point of impact of stimuli, such as the medical diagnosis, as ia our study. However, longer term distress states (e.g., depression measured at multiple time points) have also been related to subsequent decline in CD4 number (Burack et al., 1992; Kemeny, cited in Solomon, Kemeny, & Tern- oshok, 1991), which one expects may be related to further disease progres- sion. Future work should address optimal means of capturing chronic mood disturbances as opposed to "snapshots" of affect on the day of testing. Chronic mood disturbances may reflect more accurately the person's net ability to manage the burden of the HIV infection.

The third variable related to disease progression (to AIDS/death) is treat- ment adherence. TO operationalize ongoing active coping strategies, we included here attendance, report of frequency of relaxation practice, and complet ion of s tress-management homework assignments. What is the mechanism by which adherence may be related to slower disease progres- sion? A first possibility is that people with better attendance at the interven- tion may also be more conscientious about taking medications such as AZT----a possibility that could be empirically determined in futu~:e research.

102 IRONSON ET AL,

Because our subjects were recruited before they knew their antibody status and remained asymptomatic during the initial 10-week observation period, we could not use changes in antiviral use as an intermediary variable. It is possible that both adherence/participation in interventions and taking medi- cations may be a reflection of an underlying personality trait labeled consci- ent iousness--a variable that has been identified as a major personality variable (Costa & McCrae, 1988; Digman, 1990; Digman & lnouye, 1986) but that is largely unexplored in the context of health and behavior. A second possibility is that people who came to the intervention simply got more out of it. The CBSM intervention, for example, did buffer the distress of seropos- itive notification (Antoni, Baggett, et al., 1991)--which was the main pur- pose of the intervention--and was associated with decreases in maladaptive coping strategies such as denial (Antoni et al., 1992). More specifically, a greater frequency of relaxation practice in the weeks preceding diagnosis predicted lower postnotification distress scores after controlling for pre- notification distress (Anloni, Baggett, et al., 1991). We are currently incor- porating additional manipulation checks Io our intervention in order to ascertain changes in cognitive distortions, negative thinking, and safer sex behaviors. Thus, it may be through changes in these phenomena thai adher- ence/participation has an impact on disease progression.

Last, there were no differences among treatment groups (CBSM, AE, control) in the incidence of disease progression. Conclusions about group effects are obviously limited by the small sample size (and thus limited statistical power) and by the differential dropout rate (we lost none of the 9 CBSM subjects who completed the first 10 weeks [or the 2-year follow-up and none of the 9 exercisers, but 4 of the 9 controls). Some controls lost to follow-up may have died. Even if the interventions do not affect disease progression directly, they may indirectly influence behavioral variables as- sociated with disease progression (e.g., substance use, exposure to new STDs via unprotected sexual behaviors). Although there were no main ef- Iects of the interventions on disease progression, the interventions do have an impact on variables related to disease progressions-distress (Antoni, Baggett, el. al., 1991; LaPerriere et al, 1990) and denial (Antoni et al., 1992). Just as previous research has shown one must often look at subjects within groups (Kiecolt-Glaser et al., 1986), the current research suggests as well that individual gains within interventions may be more important than group assignment alone. Future work should explore how these interventions may enhance quality of life, a sense of self-efficacy, and maintenance of social support, which in turn may relate to health outcomes.

CONCLUSIONS

The present study is the first to demonstrate significant relations between psychological variables on the one hand and both immune measures and HIV-1 disease progression on the other. Although the sample size is small,

1 0 3

there appear to be several factors that may have contributed to a sensitive assessment. First, subjects were asymptomatic at the onset of the study. Second, they were unaware of their HIV-1 serostatus. Third, the study was able to examine important psychological responses (i.e., distress, denial) to serostatus nol i f ieat ion--a major psychological stressor. Fourth, the study was able to assess, in a meaningful way, adherence to a therapeutic regime. Based on these factors, we were able to document that distress upon diagno- sis, denial increase surrounding diagnosis, and low adherence/participation were each strongly positively related to disease progression.

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