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Our Lady of the Way Hospital, like most hospitals in the late 1980s and early 1990s, exemplified the bureaucratic organization represented by the traditional "line and box organization chart." Additionally, as in most small hospitals, the CEO of Our Lady of the Way Hospital--a 39-bed, JCAHO accredited, general, acute care hospital in Martin, Kentucky--had direct management responsibility for several functional departments. In 1992, administration replaced the traditional, hierarchical organization chart with a circular structure that reflected its increased reliance on team processes throughout the organization. The new structure also significantly reduced the number of reporting assignments to the CEO. This article describes the hospital's transition to a team-based organization, illustrates the application of a circular organization chart, and assesses its value and limitations.

Background: Bacteremia with the Mycobacterium avium complex is common in patients with the acquired immunodeficiency syndrome (AIDS), but the most effective treatment for this infection remains unclear., Methods: We randomly assigned 229 patients with AIDS and M. avium complex bacteremia to receive either rifampin (600 mg daily), ethambutol (approximately 15 mg per kilogram of body weight daily), clofazimine (100 mg daily), and ciprofloxacin (750 mg twice daily) (the four-drug group) or rifabutin (600 mg daily), ethambutol (as above), and clarithromycin (1000 mg twice daily) (the three-drug group). In the three-drug group the dose of rifabutin was reduced by half after 125 patients were randomized, because 24 of 63 patients had uveitis., Results: Among 187 patients who could be evaluated, blood cultures became negative more often in the three-drug group than in the four-drug group (69 percent vs. 29 percent, P<0.001). Among patients treated for at least four weeks, the bacteremia resolved more frequently in the three-drug group (78 percent vs. 40 percent, P<0.001). In the three-drug group, bacteremia resolved more often with the 600-mg dose of rifabutin than with the 300-mg dose (P=0.025), but the latter regimen was more effective than the four-drug regimen (P<0.05). The median survival was 8.6 months in the three-drug group and 5.2 months in the four-drug group (P = 0.001). The median Karnofsky performance score was higher in the three-drug group than in the four-drug group from week 2 to week 16 (P<0.05). Mild uveitis developed in 3 of the 53 patients receiving the 300-mg dose of rifabutin, an incidence about one quarter that observed with the 600-mg dose (P<0.001)., Conclusions: In patients with AIDS and M. avium complex bacteremia, treatment with the three-drug regimen of rifabutin, ethambutol, and clarithromycin leads to resolution of the bacteremia more frequently and more rapidly than treatment with rifampin, ethambutol, clofazimine, and ciprofloxacin, and survival rates are better.

Zidovudine is a dideoxynucleoside analogue of thymidine. It acts by interfering with viral reverse transcriptase, thereby inhibiting human immunodeficiency virus (HIV) replication. Zidovudine has been shown in clinical trials to prolong survival of patients with acquired immune deficiency syndrome (AIDS) and advanced AIDS-related complex (ARC), and to delay progression to ARC or AIDS in patients with earlier disease. At the present time it is suggested that zidovudine be initiated when the CD4 lymphocyte count is less than 500 cells/mm3. Recent studies have suggested a delay in the development of AIDS in patients with CD4 counts over 500 cells/mm3, but ongoing studies will require confirmation. The adverse reactions associated with zidovudine have been well described. It appears that haematological toxicity is associated with both the dose and stage of disease. Anaemia may present more often within the first 3 months of therapy, whereas neutropenia can occur early or late. Mild headache and gastrointestinal intolerance may occur early and in some cases limit tolerance to the drug. A number of neurological adverse reactions have been reported rarely including seizures and dose-reduction encephalopathy. The most significant late adverse reaction is that of myopathy, which occurs in patients receiving zidovudine for more than 6 months. With careful monitoring, the adverse reactions of zidovudine are manageable and patient tolerance of the medication is acceptable.

The Toronto Sexual Contact Study comprises a cohort of 249 male sexual contacts of men with HIV disease which has been followed every 3 months for almost 5 years. On enrollment 143 were seropositive and 16 seroconverted during the follow-up period. By 31 December 1989, 41 of the 159 seropositive cohort members had developed AIDS. Using Cox relative risk regression models, we investigated the association of a number of laboratory and clinical variables and progression to AIDS. Fixed covariate models examined laboratory variables from the enrollment visit of cohort members, with time calculated from this date. In models assessing time dependent covariates, time was calculated from the estimated date of HIV infection. In the univariate models of either fixed or time dependent covariates, many variables were significantly associated with risk of progression to AIDS (T4 cell count, T4/T8 ratio, blastogenic responses to phytohemagglutinin, concanavalin A, and pokeweed mitogen, serum IgA, appearance of p24 antigen, and the development of oral hairy leukoplakia, thrush, or herpes zoster). Appearance of persistent generalized lymphadenopathy was not associated with increased risk of progression. In the multivariate model which evaluated fixed laboratory covariates, T4/T8 ratio, IgA level, and PHA response at enrollment were significantly associated with elevated risk.(ABSTRACT TRUNCATED AT 250 WORDS)

In a cohort of 249 male sexual contacts of men with AIDS or an AIDS-related condition (ARC), 143 cohort members were seropositive on enrollment and 16 seroconverted during follow-up. A logistic Weibull mixture model was used to estimate the probability of progression to AIDS after HIV infection when infection was assumed to occur during the period of sexual contact with the primary case. Forty cohort members developed AIDS while under study. It appears that at least 50% of men with HIV disease will progress to AIDS and that the best estimate of this probability lies anywhere in the interval 70% to 100%.

We describe the sexual behaviour reported by 240 seronegative and seropositive homosexual men over a 3-year period. Sexual partners of men with HIV disease were recruited into a prospective study between July 1984 and July 1985 and were monitored every 3 months thereafter. Data on sexual activities were collected through interviewer-administered questionnaires. The cohort experienced a reduction in both the number of sexual partners and the volume of sexual activity. Reductions in the number of partners were early and dramatic. Changes in sexual activities were gradual and consistent in trend. The greatest reduction occurred in high risk activities (receptive and insertive anal intercourse). After 3 years of follow-up, only 10% of the men continue to be exposed to semen through unprotected receptive anal intercourse and 18% through unprotected receptive oral-genital sex. The proportion of men engaging in oral-genital contact and masturbation remained stable over the 3 years. Once informed of their serostatus, both seropositive and seronegative men reduced their high risk behaviour. The decline in rates of STDs and seroconversion confirmed that this cohort had indeed reduced their high risk behaviour.

HIV antigen detection kits are available from a number of commercial sources. Abbott, Coulter, and Du Pont antigen kits were used to test 661 sera collected sequentially from 65 members of the Toronto Sexual Contact Study (TSCS). The sera had been collected at 3-month intervals over 4 years from nine persistently HIV-seronegative men, 14 seroconverters, and 42 seroprevalent participants. Antigen was not detected in any seronegative men. Two of 14 seroconverters were antigen positive in the specimen immediately preceding seroconversion (by all kits). Antigen was detected in 22 of 56 seropositive participants; of these, 16 of 22 demonstrated the emergence of antigen during observation. Discrepancies were noted in the time of detection of antigen (ranging from 3 months to more than 3 years) in nine participants. Although overall concordance among all kits for all specimens appears high (95.4%), when the bias introduced by testing multiple specimens from the same patient is removed, the lower bound of concordance among all three kits is estimated to be 80%. Similarly, after correction, the upper and lower bound of estimates of sensitivity are Abbott 96, 92%; Coulter 88, 63%; and Du Pont 88, 58%. There are significant differences in the performance characteristics of these commercial products for the detection of HIV antigen in serum.

Cytomegalovirus (CMV) retinitis is the most common cause of blindness in AIDS. Twenty patients were treated with a 21-day course of foscarnet therapy by continuous infusion. Response to therapy was good in eight (47%) of 17 evaluable patients; partial arrest of progression was observed in eight (47%); and no response was obtained in one (6%). Foscarnet therapy did not lead to suppression of urinary excretion of CMV in four of 12 patients who nonetheless had improvement in retinal lesions. Toxic effects, especially reversible renal failure, were common, with blood creatinine increase in 50% and dialysis in two patients. Renal toxicity occurred primarily during the third week of therapy. Anemia (hemoglobin less than 80 g/L) occurred in 10 patients after a mean of 14.5 +/- 5.1 days of therapy and required transfusion. Review of this study and of data from a previous case series, however, was inconclusive regarding the additional benefit of a third week of therapy. Maintenance therapy was given to seven patients. Four had recurrence of CMV retinitis at a mean interval of 62 +/- 52 days. Only one patient has maintained prolonged remission on maintenance (greater than 24 weeks). Toxicity on the maintenance protocol included anemia (two of seven patients) and increased creatinine blood levels (one of seven patients). Zidovudine therapy in six patients did not contribute to increased toxicity of induction or maintenance therapy. Drug levels during continuous infusion were stable for individual patients but showed wide inter-patient variability. Peak levels of post-maintenance infusion varied both within and between patients.

Thirteen men with a median age of 37 (range 28 to 46) years who had extensive Kaposi's sarcoma associated with acquired immune deficiency syndrome (AIDS) were treated with combination chemotherapy and alpha-interferon. Four patients had stage III disease and nine had stage IV disease (one with pulmonary and eight with gastrointestinal involvement). Treatment consisted of monthly courses of actinomycin D, 1 mg/m2, and vinblastine sulfate, 6 mg/m2, given intravenously on day 1, bleomycin, 10 mg/m2 given intravenously on days 1 and 8, and human lymphoblastoid (alpha-) interferon, 10 million U/m2 given subcutaneously three times a week for six doses starting on day 14. Forty-one treatment cycles (median 3, range 1 to 12) were administered. The median granulocyte and platelet counts on day 14 before the start of interferon therapy were 600 X 10(9)/L and 134 X 10(9)/L respectively; the counts did not fall further during interferon therapy. There was no difference in T-cell subsets, 2',5'-oligoadenylate synthetase level or results of blastogenesis studies after interferon therapy. Four patients required admission to hospital for neutropenia-associated fever. A complete response (of 24 weeks' duration) was seen in one patient and a partial response (of 14 to 44 weeks' duration) in four. One patient had a mixed response, with regression of skin involvement but progression of pulmonary disease. The median length of survival was 48 (range 4 to 143) weeks. Eleven patients died of progressive Kaposi's sarcoma, one of lymphoma and one of Pneumocystis carinii pneumonia. The results suggest that this form of therapy is not appropriate for patients with Kaposi's sarcoma associated with AIDS.

The influence of genetic factors on the modulation of hepatosplenomegaly, portal venous pressure and granuloma size in chronic murine schistosomiasis mansoni was studied. Experiments with congenic mice confirmed previous observations that after 8 weeks of infection these disease manifestations are influenced by non-H-2 genes. During chronic infection (20 weeks compared to 8 weeks of infection), hepatosplenomegaly was minimally altered. Portal venous pressure was found to increase in 129/J and BALB/cJ mice, did not change in C57BL/6J and DBA/2J and decreased in CBA/CaJ mice. Simultaneous measurements of granuloma size delineated two groups: decrease of greater than 40%--C57BL/6J, DBA/2J and CBA/CaJ strains and decrease of less than or equal to 20%--129/J, BALB/cJ and C3H/HeJ mice. There was no consistent correlation between the magnitude or direction of alterations in portal pressure and granuloma size among the various strains studied. Furthermore, these alterations were independent of changes in parasite burden (adult worms or hepatic eggs). This amelioration of disease (modulation) was found to be influenced by a small number of non-H-2 genes.

This study compared clinical and laboratory parameters in 37 individuals with serologic evidence of exposure to human T-cell lymphotropic virus type 3 (HTLV-III) and generalized lymphadenopathy. Basal levels of the interferon-induced enzyme, 2-5A synthetase were also measured and compared with the clinical parameters. A significant linear relationship (p less than .05) was demonstrated between the logarithm of the basal synthetase level and both the number and size of palpable nodes in the posterior cervical triangles of the men studied. No other lymph node chains demonstrated such a relationship. In addition, men with more than 3 palpable nodes (the median number) in the posterior triangles had lower mean levels of lymphocytes, reduced mean mitogen responses to PWM, PHA, and ConA, elevated mean levels of IgG, IgA, and IgM, and were more frequently anergic on skin testing. These findings suggest the need for further longitudinal study of the possibility that extent of lymphadenopathy and level of 2-5A synthetase might serve as useful parameters to monitor disease activity.

A cohort of 61 patients with Kaposi's sarcoma (KS) and AIDS was seen in the Oncology Unit of the Toronto General Hospital between 1982 and 1986. In an attempt to identify prognostic variables, laboratory and clinical parameters were examined using Kaplan-Meier estimates and the Cox Regression Model. All patients were male, median age 36 years (range 23-52). In 49 patients KS was diagnosed before any AIDS-associated opportunistic infection (OI). Three patients had concurrent KS and OI, and nine patients developed KS one or more months after an OI. Only 11 patients had stage I or II disease, 34 stage III, and 15 stage IV. Only 18 patients (30%) were asymptomatic. Twenty-six percent had fever, night sweats, or weight loss, 11% had minor opportunistic infections, and 33% had both symptom complexes. The median overall survival was 10.5 months. The survival of patients who received chemotherapy for their KS was not significantly different from the survival of non-treated patients (p = 0.7). Although significant differences in survival could not be seen between stages, patients with both systemic symptoms and minor opportunistic infections had significantly shorter survival (p = 0.03). Survival from the onset of KS was significantly shorter for patients who had experienced a previous OI, but their overall survival from the date of diagnosis of AIDS was not significantly different from those patients presenting with KS alone. When analyzed separately the laboratory parameters of hemoglobin (p less than 0.0001), absolute lymphocyte count (p = 0.03), platelet count (p = 0.04), and T4 level (p = 0.05) demonstrated a significant relationship with survival.(ABSTRACT TRUNCATED AT 250 WORDS)

The microfilaricidal effect of diethylcarbamazine was studied in the murine model of Brugia malayi microfilaremia. CFI mice with circulating microfilariae were treated with either diethylcarbamazine (6 mg kg-1 day-1) for 10 days or with normal saline. Although antibodies against crude microfilarial antigen were detected in both groups at the time of completion of therapy, the chemically induced microfilarial clearance occurred prior to the development of these antibodies. In addition, the passive transfer of antibody just prior to chemical treatment did not enhance diethylcarbamizine-induced microfilarial clearance. In vitro studies confirmed previous observations that diethylcarbamazine enhanced antibody-dependent neutrophil adherence. Microfilarial clearance was found to be due to trapping and lysis in the liver on pathologic examination. These studies demonstrate that diethylcarbamazine leads to microfilarial clearance in the liver by mechanisms that are not dependent on host antibody.

Genetic dependence of susceptibility to primary infection with Schistosoma mansoni was studied in inbred strains of mice. Eight weeks after the subcutaneous injection of 30 cercariae, C3H/HeJ (H-2k), DBA/1J (H-2q) and BALB/cJ (H-2d) had the highest number of adult worms per animal (8.0-9.8); DBA/2J (H-2d) and 129/J (H-2b) had an intermediate number (6.2-6.4); C57BL/6J (H-2b), BUB/BnJ (H-2q) and CBA/CaJ (H-2k) had the lowest number (3.4-4.0). Studies in congenic mice further suggested that genes within the major histocompatibility complex do not have a major influence on determining the ability of schistosomes to develop into mature adult worms. Results of experiments in which adult worm loads in the F1 generation of C57BL/6J X BALB/cJ were compared with F1 X C57BL/6J and F1 X BALB/cJ backcrosses are consistent with homozygosity for a polygenic phenomenon controlling susceptibility to primary S. mansoni infection. Strain associated differences in parasite development appeared to be related to host defense processes directed against maturing adult worms.

Lymphocyte blastogenic responses to O. volvulus antigen (Oncho Ag), SKSD, and the mitogen PHA were tested in three groups of persons: light to moderately infected persons (INF); previously exposed but uninfected persons (EXP) and normal controls (NC). The exposed group showed significant responsiveness to Oncho Ag (delta ct/min = 6,002 +/- 1,375), while the infected (delta ct/min = 943 +/- 418) and normal control (delta ct/min = 428 +/- 418) groups did not. The mean blastogenic response to SKSD were EXP, 8,644 +/- 5,249; NC 6,039 +/- 2,880; INF, 2,619 +/- 1,012. The reduced reactivity in the INF group to Oncho Ag showed a significant correlation with reactivity to SKSD (P less than 0.05). To elucidate the mechanism of hyporesponsiveness in the infected group rigorous adherent cell depletion, by adherence to plastic followed by a nylon wool column, was utilized. When 20% plastic adherent cells were added back to the T cells prepared in this fashion, the mean blastogenic response to SKSD was significantly augmented (P less than 0.01). In contrast, the responsiveness to Oncho Ag was not significantly altered. The addition of indomethacin (1 microgram/ml) or autologous plasma had no significant effect on reactivity to either SKSD or Oncho Ag. There were no significant differences in the mean reactivity of the three groups to PHA-M (delta ct/min EXP 78,514 +/- 12,564; INF 62,393 +/- 14,447; NC 61,423 +/- 4,465). These results suggest that O. volvulus infection is associated with decreased lymphocyte reactivity to both parasite related and unrelated antigens, and imply that the mechanism for the two types of hyporesponsiveness may be distinct. While a weakly adherent suppressor cell may account for non-specific hyporesponsiveness, the mechanism of parasite specific decreased reactivity remains unknown.

A 25-year-old man with hemophilia who had been treated primarily with cryoprecipitate presented with epigastric pain and loose, melenic stools. He had a long history of malaise and intermittent upper respiratory tract infection with fever. The patient was shown to have disseminated histoplasmosis and refractory herpes simplex. Immunologic studies demonstrated a markedly decreased ratio of helper to suppressor T cells, lymphopenia, cutaneous anergy and a slightly elevated serum IgA level. These findings met the criteria for the diagnosis of acquired immune deficiency syndrome. In addition, antibodies to human T-cell leukemia virus were detectable in the serum.

The levels of the 2'-5' oligoadenylate enzyme synthetase in extracts of peripheral blood mononuclear cells from individuals with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC) were measured and compared with synthetase levels in peripheral blood mononuclear cells (PBMs) from healthy heterosexual and homosexual controls. The mean basal synthetase level in heterosexual and homosexual controls was 14 +/- 13 and 12 +/- 9 pmol per hr/10(5) PBMs, respectively. Thirteen individuals with AIDS had a mean basal level of 129 +/- 75 pmol. Serial levels were persistently elevated in six of these individuals over a one- to 10-month period. Twelve of the 13 individuals had antibodies to human T cell lymphotrophic virus-III/lymphadenopathy-associated virus (HTLV-III/LAV). Thirty-three individuals with ARC had a mean basal synthetase level of 68 +/- 84 pmol. Thirty-two of the 33 had antibodies to HTLV-III/LAV. Eleven (33%) have had consistently normal synthetase levels (less than 2 SD above the mean for the homosexual controls, i.e., 30 pmol) over a three- to nine-month follow-up period. Fourteen (42%) had persistently elevated levels over the same period; four (29%) of these developed AIDS during the follow-up period. Eight have had fluctuating levels but have remained clinically well. These studies suggest that persistently elevated synthetase levels in individuals with ARC and antibodies to HTLV-III/LAV indicate progressive virus-induced disease activity. Elevated synthetase levels may be an important prognostic indicator of increased risk of progression to AIDS.

Human as well as murine granulocytes have been shown to kill the larval stages of helminth parasites; the mechanism of this cell-mediated cytotoxicity is, however, poorly understood. The present study was designed to assess the role of peroxidative processes in killing of schistosomula of Schistosoma mansoni by human granulocytes in vitro. The rate of H(2)O(2) production by human neutrophils, eosinophils, and basophils was measured upon incubation with schistosomula alone or in the presence of specific antibody or complement. Opsonized parasites (antibody and/or complement) increased the rate of H(2)O(2) production by neutrophils, eosinophils, and basophils by respective percentages of 500, 500, and 371. The rate of H(2)O(2) release was directly related to the number of granulocytes and to the proportion of cells attached to the surface of the schistosomula. Increased hydrogen peroxide release occurred by 10 min of incubation and was demonstrable up to 16 h after addition of leukocytes to schistosomula. The primary source of this oxygen product was found to be the granulocytes adherent to the schistosomula and not those that remained unattached. Hydrogen peroxide production by neutrophils and eosinophils was quantitatively similar (schistosomula coated with antibody plus complement stimulated 5 x 10(6) neutrophils and eosinophils to release H(2)O(2) at respective rates of 0.35 and 0.40 nmol/min). Granulocyte-mediated parasite killing correlated with rate of H(2)O(2) generation; both processes were inhibited by catalase. To define further the role of oxidative metabolites, neutrophils and eosinophils of two subjects with chronic granulomatous disease were used; marked reduction of granulocyte-mediated parasite mortality was observed. Peroxidase was required for H(2)O(2)-mediated killing. Addition of the peroxidase inhibitors azide (1 mM), cyanide (1 mM), or aminotriazole (1 cM) to neutrophilschistosomula mixtures significantly reduced parasite cytotoxicity (P < 0.01); similar reduction was observed when eosinophils were used (P < 0.01). Fixation of halide (iodide) to trichloroacetic acid-precipitable protein (2.4-6.0 nmol/h per 10(7) neutrophils) was demonstrated in the presence of granulocytes, opsonins, and parasites; this process was completely inhibited by 1 mM azide. These data indicate that contact between the surfaces of human granulocytes and schistosomula results in release of cellular hydrogen peroxide and iodination. The generation of H(2)O(2) and its interaction with peroxidase appear to be crucial in effecting in vitro granulocyte-mediated parasite cytotoxicity.

The effect of nonspecific activation of host macrophages by Propionibacterium acnes ("Corynebacterium parvum") or Mycobacterium bovis BCG on Brugia malayi microfilariae was determined by in vitro and in vivo studies. Intraperitoneal injection of C. parvum or BCG stimulated peritoneal exudate cells, which were toxic to microfilariae. Microfilariae were equally susceptible to damage by C57BL/6J or BALB/cJ peritoneal exudate cells. Furthermore, inhibitors of oxidative metabolism and arginine supplementation did not prevent this toxicity, suggesting that the mechanism of microfilarial damage differs from that seen with another multicellular helminth, Schistosoma mansoni. In vivo studies with both BCG and C parvum, however, did not confirm the importance of nonspecific immunity in resistance to B. malayi microfilaremia. Despite the lack of biologic relevance of this phenomenon, in vitro studies may yield important knowledge about the mechanisms of microfilarial damage.

The influence of host genetics on susceptibility of mice to Brugia malayi microfilariae and its possible mechanism were studied. There was a strain-association for duration and peak level of microfilaraemia: CBA/CaJ, C3H/HeJ, DBA/1J, AuSs/J and A.S.w/Sn had a short duration (3-5 days) and low parasitemia (19-26 parasites/100 microliters blood) compared to C57Br/cdJ, AKR/J, C57BL/6J, 129/J, BALB/cJ, DBA/2J, B10.D2/NSn, B10.D2/OSn and SJL/J (duration of 58-73 days, peak parasitaemia of 58-74 parasites/100 microliters blood). Relative resistance to microfilariae was not related to the H-2 complex as determined in studies of congenic C3H.B10 (H-2b) and B10.H-2k mice and their background strains. This trait was inherited in a dominant fashion and involved a single or small number of genes. Serum anti-microfilarial antibodies reached highest levels in strains with a long duration compared to those with a short duration of parasitaemia (geometric mean titres of 1:13450 vs 1:284). The distribution of 51Cr-labelled microfilariae among the livers, spleens, lungs and kidneys of a resistant (CBA/CaJ) and a susceptible (C57BL/6J) strain was similar. Transfer of immune lymphoid cells or sera between histocompatible (H-2k) resistant CBA/CaJ mice and susceptible C57Br/cdJ animals did not alter the duration of microfilaraemia.

The influence of genetic factors on the manifestations of disease associated with infection with Schistosoma mansoni (portal hypertension, liver granulomas, hepatosplenomegaly) and their modulation were studied in inbred strains of mice. Three groups were identified according to the degree of portal hypertension: high (portal venous pressure, 19.1 cm H2O: DBA/1J), intermediate (8.9-13.4 cm H2O; BALB/cJ, DBA/2J, CBA/CaJ, C3H/HeJ, and BUB/BnJ), and low responders (6.1 cm H2O; C57BL/6J). Granuloma size, organomegaly, and portal venous pressure were strain dependent and not H-2 dependent and were determined by more than one gene. Studies of schistosomiasis in the F1 generation of high and low responders indicated that more than one gene is involved. Modulation of portal venous pressure between eight and 20 weeks of infection occurred in C57BL/6J but not in BALB/cJ mice and was transferable with immune lymphoid cells. These data indicate that disease associated with infection with S. mansoni and its modulation in mice are influenced by the genetic (non-H-2) background of the host and dependent in part on cell-mediated immunity.

A total of 246 healthy male sexual contacts of men with either acquired immunodeficiency syndrome (AIDS) or an AIDS-related condition were recruited into a prospective study in Toronto, Canada between July 1984 and July 1985. At induction, data were collected on the sexual relationship between the contact and his primary case, sexual activities with other men, history of sexually transmitted diseases and other diseases, and use of recreational drugs. At recruitment, 144 sexual contacts had antibodies to human immunodeficiency virus (HIV); 102 of the contacts were seronegative at induction and at three months following recruitment. No association between HIV seropositivity and total number of sexual partners could be demonstrated. In univariate and multivariate analyses, receptive and insertive anal intercourse with the primary cases, and activities which either indicated or potentially caused anorectal mucosal injury (rectal douching, perianal bleeding, receipt of objects in ano, and receptive fisting) were strongly associated with HIV seropositivity. In the final multiple logistic regression model, two significant interaction effects were observed: the interaction between receptive anal intercourse and insertive anal intercourse and that between receptive anal intercourse and the anorectal mucosal injury index. These two interaction terms had negative regression coefficients which suggested that change in one sexual activity would not decrementally reduce risk of HIV infection without a comparable modification in the other activity. No association could be demonstrated between oral-genital and oral-anal sexual contact and odds ratios for these sexual activities declined to levels below 1.0 when adjusted for frequency of receptive anal intercourse.