The impact of improved self-efficacy on HIV viral load and distress in culturally diverse women living with AIDS: the SMART/EST Women's Project.

The purpose of the present study was to determine whether changes in self-efficacy over time would be related to changes in disease progression markers (CD4, viral load) in a sample of women with AIDS. A self-efficacy measure was developed and two sub-scales emerged via factor analysis of 391 HIV-positive women: AIDS Self-efficacy and Cognitive Behavioral Skills Self-efficacy. Subsequently, the sub-scales and an additional adherence self-efficacy item were given to 56 HIV-positive women who were measured at two time points three months apart. Half of these women were randomly assigned to a CB intervention and half to a low intensity comparison condition. Increases in AIDS Self-efficacy over the three-month period were significantly related to increases in CD4 and decreases in viral load. Similarly, increases in Cognitive Behavioral Skills Self-efficacy were significantly related to decreases in distress over time. Findings were maintained within the intervention group alone. Interestingly, increases in cognitive behavioral skills self-efficacy and increases in the self-efficacy adherence item were also significantly related to decreases in viral load. Implications of the findings and suggestions for future research are discussed.

Influencing medication adherence among women with AIDS.

This study examined the effects of a ten-session cognitive-behavioural stress management/expressive supportive therapy (CBSM+) intervention on adherence to antiretroviral medication. Although the intervention was not designed to influence adherence, it was theorized that improved coping and social support could enhance adherence. Women with AIDS (N = 174) in Miami, New York and New Jersey, USA, were randomized to a group CBSM+ intervention or individual control condition. Participants were African American (55%), Latina (18%) and Caribbean (18%) with drug (55%) and/or alcohol (32%) histories. Participants were assessed on self-reported medication adherence over seven days, HIV-related coping strategies and beliefs regarding HIV medication. Baseline overall self-reported adherence rates were moderate and related to coping strategies and HIV medication beliefs. Low adherent (80%) participants in the intervention condition increased their mean self-reported medication adherence (30.4% increase, t44 = 3.1, p < 0.01), whereas low adherent women in the control condition showed a non-significant trend (19.6% increase, t44 = 2.0, p > 0.05). The intervention did not improve adherence in this population; conditions did not differ significantly on self-reported adherence. Low adhering intervention participants significantly decreased levels of denial-based coping (F1,88 = 5.97, p < 0.05). Results suggest that future interventions should utilize group formats and address adherence using coping and medication-knowledge focused strategies.

Agonist-promoted internalization of a ternary complex between calcitonin receptor-like receptor, receptor activity-modifying protein 1 (RAMP1), and beta-arrestin.

The calcitonin receptor-like receptor (CRLR) is a seven-transmembrane domain (7TM) protein that requires the receptor activity-modifying protein 1 (RAMP1) to be expressed at the cell surface as a functional calcitonin gene-related peptide (CGRP) receptor. Although dimerization between the two molecules is well established, very little is known concerning the trafficking of this heterodimer upon receptor activation. Also, the subcellular localization and biochemical state of this ubiquitously expressed protein, in the absence of CRLR, remains poorly characterized. Here we report that when expressed alone RAMP1 is retained inside the cells where it is found in the endoplasmic reticulum and the Golgi predominantly as a disulfide-linked homodimer. In contrast, when expressed with CRLR, it is targeted to the cell surface as a 1:1 heterodimer with the 7TM protein. Although heterodimer formation does not involve intermolecular disulfide bonds, RAMP-CRLR association promotes the formation of intramolecular disulfide bonds within RAMP1. CGRP binding and receptor activation lead to the phosphorylation of CRLR and the internalization of the receptor as a stable complex. The internalization was found to be both dynamin- and beta-arrestin-dependent, indicating that the formation of a ternary complex between CRLR, RAMP1, and beta-arrestin leads to clathrin-coated pit-mediated endocytosis. These results therefore indicate that although atypical by its heterodimeric composition and its targeting to the plasma membrane, the CGRP receptor shares endocytotic mechanisms that are common to most classical 7TM receptors.

Association of calnexin with wild type and mutant AVPR2 that causes nephrogenic diabetes insipidus.

Over 155 mutations within the V2 vasopressin receptor (AVPR2) gene are responsible for nephrogenic diabetes insipidus (NDI). The expression and subcellular distribution of four of these was investigated in transfected cells. These include a point mutation in the seventh transmembrane domain (S315R), a frameshift mutation in the third intracellular loop (804delG), and two nonsense mutations that code for AVPR2 truncated within the first cytoplasmic loop (W71X) and in the proximal portion of the carboxyl tail (R337X). RT-PCR revealed that mRNA was produced for all mutant receptor constructs. However, no receptor protein, as assessed by Western blot analysis, was detected for 804delG. The S315R was properly processed through the Golgi and targeted to the plasma membrane but lacked any detectable AVP binding or signaling. Thus, this mutation induces a conformational change that is compatible with endoplasmic reticulum (ER) export but dramatically affects hormone recognition. In contrast, the W71X and R337X AVPR2 were retained inside the cell as determined by immunofluorescence. Confocal microscopy revealed that they were both retained in the ER. To determine if calnexin could be involved, its interaction with the AVPR2 was assessed. Sequential coimmunoprecipitation demonstrated that calnexin associated with the precursor forms of both wild-type (WT) and mutant receptors in agreement with its general role in protein folding. Moreover, its association with the ER-retained R337X mutant was found to be longer than with the WT receptor suggesting that this molecular chaperone also plays a role in quality control and ER retention of misfolded G protein-coupled receptors.

Newly synthesized human delta opioid receptors retained in the endoplasmic reticulum are retrotranslocated to the cytosol, deglycosylated, ubiquitinated, and degraded by the proteasome.

We have previously shown that only a fraction of the newly synthesized human delta opioid receptors is able to leave the endoplasmic reticulum (ER) and reach the cell surface (Petäjä-Repo, U. E, Hogue, M., Laperrière, A., Walker, P., and Bouvier, M. (2000) J. Biol. Chem. 275, 13727-13736). In the present study, we investigated the fate of those receptors that are retained intracellularly. Pulse-chase experiments revealed that the disappearance of the receptor precursor form (M(r) 45,000) and of two smaller species (M(r) 42,000 and 39,000) is inhibited by the proteasome blocker, lactacystin. The treatment also promoted accumulation of the mature receptor form (M(r) 55,000), indicating that the ER quality control actively routes a significant proportion of rescuable receptors for proteasome degradation. In addition, degradation intermediates that included full-length deglycosylated (M(r) 39,000) and ubiquitinated forms of the receptor were found to accumulate in the cytosol upon inhibition of proteasome function. Finally, coimmunoprecipitation experiments with the beta-subunit of the Sec61 translocon complex revealed that the receptor precursor and its deglycosylated degradation intermediates interact with the translocon. Taken together, these results support a model in which misfolded or incompletely folded receptors are transported to the cytoplasmic side of the ER membrane via the Sec61 translocon, deglycosylated and conjugated with ubiquitin prior to degradation by the cytoplasmic 26 S proteasomes.

A brief sexual barrier intervention for women living with AIDS: acceptability, use, and ethnicity.

Interventions aimed at reducing sexual transmission of human immunodeficiency virus/sexually transmitted diseases (HIV/STDs) have focused primarily on male condom use among seronegative men and women. However, female-controlled sexual barriers (female condoms and vaginal microbicides) offer women living with acquired immunodeficiency syndrome (AIDS) alternative methods to protect themselves and others from disease transmission. A pilot behavioral intervention was conducted to increase sexual barrier use and enhance and assess factors related to acceptability. Participants (N = 178) were drawn from the Stress Management and Relaxation Training with Expressive Supportive Therapy (SMART/EST) Women's Project, a multisite phase III clinical trial for women living with AIDS (Miami, FL; New York City, NY; Newark, NJ). Intervention participants (n = 89) were matched for age and ethnicity with control condition participants (n = 89). Women were African American (52%), Haitian (15%), Hispanic (19%), Caucasian (10%), and other ethnicities (4%). The intervention condition received barrier products (male and female condoms and spermicides based on nonoxynol-9 in the form of vaginal gel, film, and suppositories) during three sessions held over 3 months. Data on barrier use and acceptability were analyzed at baseline and 3 and 9 months postintervention. Use of N-9 spermicides on a trial basis increased significantly by 3 months in the intervention conditions (22%-51%, P <.05). Cultural differences in acceptability were greatest between Haitian women and women in other ethnic groups. Exposure to this pilot behavioral intervention was associated with increased acceptability and use of chemical barriers without decreased use of male condoms.

Export from the endoplasmic reticulum represents the limiting step in the maturation and cell surface expression of the human delta opioid receptor.

Synthesis and maturation of G protein-coupled receptors are complex events that require an intricate combination of processes that include protein folding, post-translational modifications, and transport through distinct cellular compartments. Relatively little is known about the nature and kinetics of specific steps involved in these processes. Here, the human delta opioid receptor expressed in human embryonic kidney 293S cells is used as a model to delineate these steps and to establish the kinetics of receptor synthesis, glycosylation, and transport. We found that the receptor is synthesized as a core-glycosylated M(r) 45,000 precursor that is converted to the fully mature M(r) 55,000 receptor with a half-time of about 120 min. In addition to trimming and processing of two N-linked oligosaccharides, maturation involves addition of O-glycans containing N-acetylgalactosamine, galactose, and sialic acid. In contrast to N-glycosylation, which is initiated co-translationally and is completed when the protein reaches the trans-Golgi network, O-glycosylation was found to occur only after the receptor exits from the endoplasmic reticulum (ER) and was terminated as early as the trans-Golgi cisternae. Once the carbohydrates are fully processed and the receptor reaches the trans-Golgi network, it is transported to the cell surface in about 10 min. The exit from the ER was found to be the limiting step in overall processing of the receptor. This indicates that early events in the folding of the receptor are probably rate-limiting and that receptor folding intermediates are retained in the ER until they can adopt the correct conformation. The overall low efficiency of receptor maturation, less than 50% of the precursor being processed to the fully glycosylated protein, further suggests that only a fraction of the synthesized receptors attain properly folded conformation that allows exit from the ER. This indicates that folding and ER export are key events in control of receptor cell surface expression. Whether or not the low efficiency of the ER export is a general feature among G protein-coupled receptors remains to be investigated.

Pharmacological chaperones rescue cell-surface expression and function of misfolded V2 vasopressin receptor mutants.

Over 150 mutations within the coding sequence of the V2 vasopressin receptor (V2R) gene are known to cause nephrogenic diabetes insipidus (NDI). A large number of these mutant receptors fail to fold properly and therefore are not routed to the cell surface. Here we show that selective, nonpeptidic V2R antagonists dramatically increase cell-surface expression and rescue the function of 8 mutant NDI-V2Rs by promoting their proper folding and maturation. A cell-impermeant V2R antagonist could not mimic these effects and was unable to block the rescue mediated by a permeant agent, indicating that the nonpeptidic antagonists act intracellularly, presumably by binding to and stabilizing partially folded mutants. In addition to opening new therapeutic avenues for NDI patients, these data demonstrate that by binding to newly synthesized mutant receptors, small ligands can act as pharmacological chaperones, promoting the proper folding and maturation of receptors and their targeting to the cell surface.

Cardiopulmonary and CD4 cell changes in response to exercise training in early symptomatic HIV infection.

PURPOSE: The purposes of the present study were to assess the effects of a 12-wk laboratory based aerobic exercise program on cardiopulmonary function, CD4 cell count, and physician-assessed health status among symptomatic pre-AIDS HIV-infected individuals (N = 28) and to assess the degree to which ill health was associated with exercise relapse. METHODS: Responses to graded exercise test, physician-assessed health status, and CD4 cell counts were determined at baseline and 12-wk follow-up for participants randomly assigned to exercise or control conditions, and reasons for exercise noncompliance were recorded. RESULTS: Approximately 61% of exercise-assigned participants complied (> 50% attendance) with the exercise program, and analyses of exercise relapse data indicated that obesity and smoking status, but not exercise-associated illness, differentiated compliant from noncompliant exercisers. Compliant exercisers significantly improved peak oxygen consumption (VO2peak; 12%), oxygen pulse (O2pulse; 13%), tidal volume (TV; 8%), ventilation (VE; 17%), and leg power (25%) to a greater degree than control participants and noncompliant exercisers (all P < 0.05). Although no group differences in health status were found, a significant interaction effect indicated that noncompliant exercisers' CD4 cells declined (18%) significantly, whereas compliant exercisers' cell counts significantly increased (13%; P < 0.05). CONCLUSION: We conclude that although aerobic exercise can improve cardiopulmonary functioning in symptomatic HIV-infected individuals with minimal health risks, attention to factors associated with exercise adherence is warranted.

Aerobic circuit exercise training: effect on adolescents with well-controlled insulin-dependent diabetes mellitus.

OBJECTIVES: To test the safety and effects of exercise conditioning on cardiorespiratory fitness, body composition, muscle strength, glucose regulation, and lipid/cholesterol levels. SUBJECTS: Ten male adolescents with insulin-dependent diabetes mellitus (IDDM) and 10 adolescent nondiabetic (ND) subjects. DESIGN: Pretest, posttest intervention trial with control group. SETTING: University-based human performance laboratory. INTERVENTION: Mixed endurance and calisthenic/strength activities performed at a rapid pace three times weekly for 12 weeks. RESULTS: Only one subject with IDDM experienced hypoglycemia after a single exercise session. Both subject groups improved their cardiorespiratory endurance (p < .05). Lean body mass of IDDM subjects increased by 3.5% (p < .05). Subjects with and without IDDM lowered their percent body fat (p < .05 and .001, respectively). Strength improvement of IDDM subjects ranged from 13.7% (p < .001) to 44.4% (p < .01), depending upon the maneuver. Fasting blood plasma glucose for all subjects was unchanged by training, but glycosylated hemoglobin A1c of IDDM subjects was reduced by .96 percentage point (p < .05). Reductions of HbA1c benefitted subjects exhibiting poor preconditioning glycemic control. Low-density lipoprotein cholesterol was decreased in subjects with IDDM (p < .05), but not total cholesterol or triglycerides. CONCLUSION: Adolescents with IDDM undergoing aerobic circuit training improve their cardiorespiratory endurance, muscle strength, lipid profile, and glucose regulation. Aerobic circuit training is safe for properly trained and monitored adolescent diabetics.

Social cognitive and physical health determinants of exercise adherence for HIV-1 seropositive, early symptomatic men and women.

This study examined social cognitive and physical health factors that might explain variations in exercise adherence in a 3-month supervised exercise intervention for a group of mildly symptomatic, HIV-1 seropositive men and women. The social cognitive predictor variables were outcome expectations and self-efficacy. The physical health predictor variables included CD4+ cell counts, self-report inventories of physical symptoms, and physicians' examinations. Self-report inventories of physical symptoms were associated with physicians' examinations and combined into a composite measure of physical health. Criterion variables included exercise adherence rates, VO2max change, and status as a 'remainder' versus 'drop-out.' The composite measure of physical health emerged as a significant predictor of adherence rate and gave perfect prediction of remainers and a moderate prediction of dropouts. No significant associations were observed between the social cognitive predictors and adherence. Results suggest that for this population physical health status is a better predictor of exercise adherence than either perceived self-efficacy or outcome expectancy.

Posttraumatic stress symptoms, intrusive thoughts, loss, and immune function after Hurricane Andrew.

OBJECTIVE: To examine the impact of and relationship between exposure to Hurricane Andrew, a severe stressor, posttraumatic stress symptoms and immune measures. METHODS: Blood draws and questionnaires were taken from community volunteer subjects living in the damaged neighborhoods between 1 and 4 months after the Hurricane. RESULTS: The sample exhibited high levels of posttraumatic stress symptoms by questionnaire (33% overall; 76% with at least one symptom cluster), and 44% scored in the high impact range on the Impact of Events (IES) scale. A substantial proportion of variance in posttraumatic stress symptoms could be accounted for by four hurricane experience variables (damage, loss, life threat, and injury), with perceived loss being the highest correlate. Of the five immune measures studied Natural Killer Cell Cytotoxicity (NKCC) was the only measure that was meaningfully related (negatively) to both damage and psychological variables (loss, intrusive thoughts, and posttraumatic stress disorder (PTSD). White blood cell counts (WBCs) were significantly positively related with the degree of loss and PTSD experienced. Both NKCC (lower) and WBC were significantly related to retrospective self-reported increase of somatic symptoms after the hurricane. Overall, the community sample was significantly lower in NKCC, CD4 and CD8 number, and higher in NK cell number compared to laboratory controls. Finally, evidence was found for new onset of sleep problems as a mediator of the posttraumatic symptom-NKCC relationship. CONCLUSIONS: Several immune measures differed from controls after Hurricane Andrew. Negative (intrusive) thoughts and PTSD were related to lower NKCC. Loss was a key correlate of both posttraumatic symptoms and immune (NKCC, WBC) measures.

Change in CD4+ cell enumeration following aerobic exercise training in HIV-1 disease: possible mechanisms and practical applications.

Growing evidence suggests that routine physical activity, by individuals who are HIV-1 infected, may have significant impact on several important components of good health. Some of the physical benefits noted are: an increase in cardiopulmonary fitness, improved muscle function, and weight gain, while psychological benefits consisting of improved mood states and increased active coping behaviors have been observed. However, the emphasis of this paper is on the effects of exercise training on the enumeration of CD4+ cells in HIV/AIDS. A review of all the available literature revealed: (1) no decline in CD+ cell counts seen in any of the studies, regardless of the initial stage of disease, level of CD4+ cells, or symptomatology; (2) a trend toward an increase in the number of CD4+ cells in all but one study, with the more significant increases seen in those subjects at earlier stages of disease; and (3) the importance of homogeneous study samples when investigating the effects of exercise in a dynamic disease, such as HIV/AIDS. With regard to possible mechanisms, psychological stress has been implicated among the cofactors contributing to the immunological decline in HIV-1 disease. Good evidence was presented which supports the stress management role of exercise training as a means to explain the buffering of these suppressive stressor effects, thereby facilitating a return of the CD4+ cell count to more normal levels. We therefore believe that the observed elevation in the number of CD4+ cells actually represents a normalization of CD4+ cells. With regards to practical application, collectively these studies provide reason to encourage HIV-1 infected individuals to begin an exercise training program, preferably while they are in the early stages of disease, and in compliance with the suggested guidelines.

Psychological stress, exercise and immunity.

In terms of cardiovascular, endocrine and immune responses, acute high-intensity aerobic exercise stress may be considered as a subcategory of stressful active coping. The cardiorespiratory responses of both include increases in heart rate, cardiac output, systolic blood pressure, skeletal muscle vasodilation and oxygen consumption. Neurohormonal responses include increases in catecholamines as well as elevations in cortisol under high but relatively low sympathetic activation. Immune system responses include increases in natural killer (NK) cell number and cytotoxicity and suppressor/cytotoxic lymphocytes as well as decreased proliferative response to mitogens. Task and recovery periods for both acute psychological stress or exercise show biphasic changes in immune response such that immune status is negatively impacted during recovery. Chronic life stressors influence acute cardiovascular, endocrine and immune responses to acute stressors. In addition, both chronic stress and unusually heavy chronic exercise can negatively impact immune status. Given impaired immune status following chronic stress and interactive effects of acute and chronic stressors (e.g. blunted acute NK responses to acute stressors), it is suggested that these factors may extend the window of vulnerability for infectious agents to act following acute psychological (e.g. examinations) or strenuous exercise (competitive athletics) stressors.

Phototoxicity of some bromine-substituted rhodamine dyes: synthesis, photophysical properties and application as photosensitizers.

The synthesis of some bromine-substituted rhodamine derivatives viz., 4,5-dibromorhodamine methyl ester (dye 2) and 4,5-dibromorhodamine n-butyl ester (dye 3) are reported. These dyes were synthesized to promote a more efficient cancer cell photosensitizer for potential use in in vitro bone marrow purging in preparation for autologous bone marrow transplantation. Spectroscopic and photophysical characterization of these dyes together with rhodamine 123 (dye 1) are reported in water, methanol, ethanol and also in a microheterogeneous system, sodium dodecyl sulfate. The possible mechanism of photosensitization is characterized in terms of singlet oxygen efficiency of these dyes. Singlet oxygen quantum yields for bromine-substituted dyes are in the range of 0.3-0.5 depending on the solvent. For dye 1 no singlet oxygen production is found. The photodynamic actions of these dyes in different cell lines are tested. It was found that dye 2 and dye 3 are efficient photosensitizers and mediate eradication of K562, EM2, myeloid cell lines (CML) and the SMF-AI rhabdomyosarcoma line.

The effect of acute exercise on lymphocyte subsets, natural killer cells, proliferative responses, and cytokines in HIV-seropositive persons.

Eight healthy men infected with human immunodeficiency virus, type 1 (HIV) and eight HIV seronegative age- and sex-matched controls exercised on a bicycle ergometer (75% of VO2max, 1 h). The percentages of CD4+, CD4+45RA+, and CD4+45RO+ cells did not change, whereas the absolute number of CD4+ cells increased twofold during exercise and fell below prevalues 2 h after. The neutrophil count increase was more pronounced after exercise in the controls compared with in HIV-seropositive subjects. The percent CD16+ cells, and the natural killer (NK) and lymphokine activated killer (LAK) cell activity increased during exercise, but this increase was significantly less pronounced in the HIV-seropositive group. The results suggest that in response to physical stress, HIV-seropositive subjects have an impaired ability to mobilize neutrophils, NK and LAK cells to the blood. Furthermore, because the total number of CD4+ cells, but not the percentage of CD4+ cells, changed in response to exercise, this study further strengthens the idea that the percentage of CD4+ cells is preferable to the number of CD4+ cells in monitoring patients seropositive for HIV.

Effects of aerobic exercise training on lymphocyte subpopulations.

This study was conducted to determine the effects of an aerobic exercise training program on subpopulations of lymphocyte phenotypes. Fourteen healthy but sedentary males, 18-40 years of age, were randomly assigned to either an aerobic exercise training or control condition. Aerobic exercise training consisted of three 45-minute sessions of cycle ergometry exercise per week at 70-80% of age-predicted maximum heart rate for ten weeks. The aerobic exercise training resulted in a significant decrease in submaximal heart rate from 176 to 150 beats per minute to a fixed work rate of 150 watts (p < .01). This training effect was accompanied by increases in the resting level of the following lymphocyte subpopulations: CD2 (1717 vs 2183 mm3; p < .01), CD4 (942 vs 1280 mm3; p < .01), CD45RA+CD4+ (312 vs 595 mm3; p < .01), CD8 (655 vs 816 mm3; p < .05), and CD20 (162 vs 244 mm3; p < .01) cell counts. These findings indicate that several lymphocyte subpopulations are increased following a 10-week program of aerobic exercise training.

Specific expression of the human CD4 gene in mature CD4+ CD8- and immature CD4+ CD8+ T cells and in macrophages of transgenic mice.

The CD4 protein plays a critical role in the development and function of the immune system. To gain more insight into the mechanism of expression of the human CD4 gene, we cloned 42.2 kbp of genomic sequences comprising the CD4 gene and its surrounding sequences. Studies with transgenic mice revealed that a 12.6-kbp fragment of the human CD4 gene (comprising 2.6 kbp of 5' sequences upstream of the transcription initiation site, the first two exons and introns, and part of exon 3) contains the sequences required to support the appropriate expression in murine mature CD4+ CD8- T cells and macrophages but not in immature double-positive CD4+ CD8+ T cells. Expression in CD4+ CD8+ T cells was found to require additional regulatory elements present in a T-cell enhancer fragment recently identified for the murine CD4 gene (S. Sawada and D. R. Littman, Mol. Cell. Biol. 11:5506-5515, 1991). These results suggest that expression of CD4 in mature and immature T-cell subsets may be controlled by distinct and independent regulatory elements. Alternatively, specific regulatory elements may control the expression of CD4 at different levels in mature and immature T-cell subsets. Our data also indicate that mouse macrophages contain the regulatory factors necessary to transcribe the human CD4 gene.

Exercise and psychoneuroimmunology.

Psychoneuroimmunology is the study of the interrelationships among psychological, neuroendocrine, and immunological parameters and is concerned with how these relationships may affect an individual's health. Substantial evidence indicates that exercise is associated with improvements in mental health, neuroendocrine, and immune functioning. We synthesize these effects of exercise and propose an "exercise and psychoneuroimmunology" model by which exercise may benefit the psychologic and immunologic sequelae of several chronic diseases. For the past several years we have been investigating exercise training interventions, based on our model, for individuals infected with the human immunodeficiency virus type 1 (HIV-1). These studies indicate that a moderate exercise training program may attenuate the adverse stressor-induced psychologic and immunologic changes for asymptomatic HIV-1 seropositive individuals. In addition, our research indicates that continued aerobic exercise training may result in increased CD4 cell counts, immune surveillance, and a potential for a slowing of disease progression. Other researchers have demonstrated similar beneficial effects of exercise for individuals infected with HIV-1 who are at more advanced stages of disease. Exercise within the context of psychoneuroimmunology appears to be a very promising approach to the treatment of illness and promotion of health.

Distress, denial, and low adherence to behavioral interventions predict faster disease progression in gay men infected with human immunodeficiency virus.

This study examined psychological prediction of 2-year disease progression in gay men after finding out their human immunodeficiency virus (HIV) serostatus. 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 notification. The men were randomly assigned to an exercise. cognitive-behavioral stress-management intervention, or control group. At 2-year follow-up for the 23 men who turned out to be seropositive. 9 had developed symptoms, including 5 with acquired immune deficiency syndrome--4 of whom died. Distress at diagnosis, denial (5 weeks post-diagnosis minus pre-diagnosis). and low adherence during interventions were significant predictors of 2-year disease progression. Denial and adherence remained significant predictors of disease progression even after controlling for CD4 number at entry. Furthermore. change in denial was significantly correlated with immune status 1 year later; l-year immune status was significantly correlated with 2-year disease progression. The present study therefore demonstrates significant relations between psychological variables on the one hand and both immune measures and HIV-1 disease progression on the other. We conclude that distress, denial, and low protocol compliance predict subsequent disease progression.