Clinical manifestations of acute infection with human immunodeficiency virus in a cohort of gay men.

During a prospective study of the natural history of human immunodeficiency virus (HIV) infection in a cohort of gay/bisexual men, information on self-reported symptoms lasting for 3 or more days during the previous 6 months was collected without knowledge of the subject's HIV serological status. Twenty-two people were retrospectively found to have seroconverted to HIV during the interval. Each seroconverter was matched to two seronegative and two seropositive controls. Matched case-control analyses using the seronegative controls determined that the following symptoms lasting for 3 or more days were associated with new HIV infection: fever greater than 37.7 degrees C, swollen lymph nodes, night sweats and headaches. Matched case-control analyses using the seropositive controls determined that the following symptoms lasting for 3 or more days were associated with new HIV infection: fatigue, fever greater than 37.7 degrees C, swollen lymph nodes, night sweats and headaches. It was notable that the majority of seroconversions were not associated with any symptoms lasting for 3 or more days. Due to their non-specificity, symptoms associated with seroconversion are not likely to have a high positive predictive value. In high risk populations, however, appearance of these symptoms may facilitate identification of early infection that may be important for studies of natural history or for optimal timing for initiating antiviral therapy.

Evidence that anoreceptive intercourse with ejaculate exposure is associated with rapid CD4 cell loss.

OBJECTIVE: To determine whether ejaculate exposure through anoreceptive intercourse is associated with rapid CD4 cell loss. DESIGN: Self-reported behavioral, demographic data and blood samples were gathered longitudinally at ten semiannual visits from individuals participating in the Multicenter AIDS Cohort Study (MACS). PATIENTS/PARTICIPANTS: A group of 937 HIV-seropositive men who were continuously followed for four to ten semiannual visits. OUTCOME MEASURES: A loss of 10% or more in CD4 cells between the first two of any three consecutive semiannual visits that was followed by a 10% or greater loss between the second and third visits. RESULTS: A period of rapid CD4 cell loss over three semiannual visits occurred in 389 of the 937 (42%) HIV-seropositive men studied. Men who reported one or more anoreceptive intercourse partners with whom they were exposed to ejaculate (RAI-E) during the 12 months immediately preceding their visits were more than twice as likely to show this rapid CD4 cell loss compared with men with no such partners. CONCLUSIONS: The association between RAI-E partnerships and rapid CD4 cell loss suggests factors associated with ejaculate exposure (e.g., sexually transmitted diseases) may hasten the clinical progression of HIV disease. It is suggested that infectious diseases, which are known to be associated with ejaculate exposure, may be the causal factor underlying the association between RAI-E partnerships and rapid CD4 cell loss in these men, although the presence of these diseases was not ascertained in these data. HIV-infected individuals should be cautioned against unprotected anoreceptive intercourse.

Factors associated with a rapid course of multiple sclerosis.

A cohort of 886 cases of multiple sclerosis (MS) who had onset between Jan 1, 1960, and Dec 31, 1969, and who were resident in 1970 in either a low-prevalence area (Los Angeles County, California, 560 cases) or in a high-prevalence area (King and Pierce Counties, Washington, 326 cases) were followed up for changes in disability status through Dec 31, 1979. Cases had to meet the modified Schumacher criteria for definite/probable MS and to have had a diagnosis of MS or equivalent by a physician. Onset year of disease was determined by onset of the earliest reported symptom. Disability status was determined at intake by an interviewer-administered questionnaire and in subsequent years by an annual mailed questionnaire (self-reported disability status). Progression to a nonambulatory status or death was significantly greater among (1) patients with an older age at onset, (2) patients with a rapid early course, (3) males, and (4) residents of Los Angeles County.

The relationship between T-cell levels and CMV infection in asymptomatic HIV-1 antibody-positive homosexual men.

To investigate the relationship between cytomegalovirus (CMV) infection and progression of HIV-1 disease, a group of 234 asymptomatic, HIV-1 antibody-positive homosexual men were examined for CMV isolation and levels of CMV IgM antibodies, CMV IgG antibodies, and CD4+ and CD8+ T-lymphocytes. CMV IgG antibodies were present in 100% and CMV IgM antibodies in 22% of the men. CMV was isolated from the semen of 45% of the men. No relationship was observed between CMV IgM antibodies and CMV in semen or CD4+ levels. CD4+ cell levels were significantly lower in those from whose semen CMV was isolated. In addition, an inverse relationship was observed between the concentration of CMV in semen and CD4+ levels. We postulate that the seminal tract may be a reservoir for systemic CMV infection in HIV-infected homosexual men. Reinfection from this or other sources may result in recurrent stimulation of HIV-1 replication and lead to a further decline in CD4+ cells. Clarification of whether persistent CMV infection is secondary to HIV-1-induced immunodeficiency or, conversely, promotes a more rapid decline in immunocompetency will require follow-up studies.

Seroconversion, sexual activity, and condom use among 2915 HIV seronegative men followed for up to 2 years.

A cohort of 2915 HIV-1-seronegative men from the four centers of the Multicenter AIDS Cohort Study (MACS) was followed at 6 month intervals for 24 months to identify men who developed antibodies to HIV-1. Two hundred thirty-two men (8%) seroconverted. The highest attack rate was among men who reported practicing both receptive and insertive anal-genital intercourse. The attack rate among men who reported practicing receptive but not insertive intercourse was 3.6 times higher than among men practicing insertive intercourse although those practicing insertive only reported 38% more different partners. Only two men seroconverted who reported not practicing analgenital intercourse in the 12 month prior to the first antibody-positive visit. Because men were followed every 6 months, one of these men could have been infected within 6 months of the actual development of HIV-1 antibodies. The seroconversion rate was significantly lower among men who reported using condoms with all their partners. The results of this study (a) reaffirm that receptive anal-genital intercourse is the major route of infection among homosexual men of HIV-1, (b) suggest that there is a low risk of HIV-1 infection to the insertive partner in anal-genital intercourse, (c) suggest that infection may rarely occur through sexual activities other than anal-genital intercourse, (d) provide evidence that condoms as currently used by men in the MACS provide significant but not complete protection against HIV-1 infection, and (e) suggest that the number of men in the homosexual community engaging in high-risk behavior is declining.

Patterns of CD4+ cell changes after HIV-1 infection indicate the existence of a codeterminant of AIDS.

Successive interval slopes of CD4+ cells each constructed from levels at three consecutive 6 month visits were compared over 3 years of follow-up among 565 persistently HIV-1 antibody-positive, 326 persistently antibody-negative, and 51 seroconverting homosexual men who had at least 500 CD4+ cells/mm3 at baseline and completed the first three 6 month visits. "Change" was defined as a difference between two successive interval slopes. Sixty-two percent of seroconverters meeting these criteria experienced a shift in one or more of their successive CD4+ interval slopes, the majority (56%) from a level slope to a negative slope (decreasing numbers of CD4+ cells), a significantly greater proportion than that observed among seronegatives (30%, p less than 0.0001). Fifty-eight percent of the seropositives maintained level interval slopes over the 3 years of follow-up. The majority (59%) of those men experiencing a shift went from a level to a negative interval slope, a significantly greater proportion than observed among seronegatives (30%, p less than 0.0001). The observed patterns of change in interval slopes are consistent with the laboratory observation that CD4+ cells must be activated to replicate HIV-1. The use of the interval slope strategy provides a method to identify a temporal focal point at which to examine possible codeterminants that trigger the production of HIV-1 and the subsequent decline in CD4+ cells.

Resistance to HIV-1 infection. Multicenter AIDS Cohort Study.

Men from the Multicenter AIDS Cohort Study were classified as "susceptible" and "resistant" to HIV infection. Resistant men were still HIV antibody negative in 1993 and were estimated to have had > 45 different anal intercourse partners (median, 92; range, 46-504) in the 2.5 years before visit 2 (1985). Susceptible men were seroconverters who were estimated to have had < 13 different anal partners (median, 4; range, 0-12). Leukocyte groups were compared between the two groups of men. Values were excluded for 12 months before the first antibody-positive visit in the susceptible men. White blood cells, polymorphonuclear neutrophils, total lymphocyte count, CD8+ percentage and number, and CD3+ and CD4+ number were higher in the resistant men. Logistic regression analyses were used to develop 50 bivariate models. Higher levels of neutrophils and CD8+ cells were included in four of the six best-fitting bivariate models, suggesting that each is associated with resistance to HIV-1 infection. These results support the hypothesis that CD8+ cells may modulate the outcome of HIV-1 exposure.

Multiple sclerosis and age at exposure to childhood diseases and animals: cases and their friends.

Eighty-eight multiple sclerosis case-friend pairs were interviewed by telephone to elicit information about early-life exposures. Available mothers were also interviewed. Risk factors included childhood diseases, exposures to animals, and residence. We found a positive association between MS and having measles at a later than usual age. Analysis of the data in the literature showed that this was the third statistically significant association between MS and later age for measles. This is consistent with the hypothesis that the pathogenesis of MS includes an age-dependent host response to measles.

Multiple sclerosis and housedogs: a case-control study.

A case-control study was conducted to examine the possible association between ownership of housedogs early in life and later development of multiple sclerosis (MS). Sixty MS patients were compared with 60 neighborhood controls matched for age, sex, and race. There was no significant difference between cases and matched controls in housedog ownership, duration of ownership, or age at first exposure to housedogs over the interval from birth to 19 years of age.

A case-control study of multiple sclerosis.

We conducted a study of 145 persons with multiple sclerosis who had been identified in a 1970 survey and 145 friend controls, to investigate whether the development of MS was associated with exposure to uncommon viruses or an older age at infection with 1 or more common viruses. The most striking finding was a strong positive association for history of infectious mononucleosis (IM), suggesting older age at exposure to Epstein-Barr virus, the most common etiologic agent of IM. We also found significant positive associations for number of different domiciles before adulthood and for visits outside the United States; both would be compatible with an increased likelihood among cases of exposures to uncommon viruses or to multiple strains of a common agent. Cases were younger at menarche, increasing the probability of viral exposure after puberty.

Genetic susceptibility to multiple sclerosis.

Previous studies of histocompatibility (HLA) types in multiple sclerosis (MS) families did not provide convincing proof of an HLA-linked susceptibility factor. In 12 families we studied, all MS cases in each family shared at least one chromosome. The probability of this occurring in the absence of genetic linkage is approximately 0.001. The estimated penetrance is 5 percent, implying that the genetic susceptibility factor may be a necessary but not a sufficient cause of MS. Additional studies are needed to identify other differences between affected and unaffected susceptible individuals.

Changes in immune response during responses in MS patients.

Changes in clinical status and in two measures of immune function were followed for 21 months (median) in 106 multiple sclerosis (MS) patients and cohabitant controls. Antibody titers to measles, cytomegalovirus, and herpesvirus 1 and 2, and leukocyte migration inhibition indexes (LMIs) to measles and streptokinase/streptodornase (SKSD) were measured at 3- to 6-month intervals and at time of exacerbation in the index case. There were 36 exacerbations in 25 patients. Mean baseline antibody titers and LMI to measles were higher in cases than in controls. No consistent changes occurred in antibody titers to any of the viruses, non in LMI to SKSD. LMIs to measles were lower in most MS patients during exacerbations than before or after exacerbations. This apparent improvement in cell-mediated immune response to measles only during exacerbations may reflect aberrant immune regulation in MS patients, response to recrudescence of a latent agent, or some other phenomenon as yet undefined.

Measles antibody titers in multiple sclerosis patients and HLA-matched and unmatched siblings.

Antibody titers to measles, cytomegalovirus, and herpesviruses 1 and 2 were compared for siblings of multiple sclerosis (MS) patients sharing two, one, and no histocompatibility antigen haplotypes with the case. Significant differences were observed only for measles. Titers were significantly lower in siblings sharing no haplotypes with the case. Within case-sibling pairs, the presence of HLA-A-A3 and/or B7 affected measles antibody titers more than the presence of MS. These findings suggest that the immune response to measles in these sibships is influenced by the presence of HLA-A-A3 and/or B7 as well as another familial factor.

Asymptomatic HIV infection does not cause EEG abnormalities: results from the Multicenter AIDS Cohort Study (MACS)

We conducted EEG testing in 200 asymptomatic homosexual men, half of whom were HIV seropositive. We chose to include half of the subjects because they were rated as impaired on a neuropsychological screening test. We used both traditional visual EEG interpretation and quantitative EEG analysis. Abnormal EEGs and borderline degrees of EEG slowing occurred in 32% of these men. These EEG changes were not related to HIV serostatus. EEG changes did correlate with the impaired neuropsychological test performance. Clinicians faced with abnormal EEG results or borderline EEG slowing in an asymptomatic HIV-seropositive patient should not attribute the EEG change to effects of the serostatus itself but should look for other causes.

HLA types and immunity in multiple sclerosis.

HLA types and levels of humoral and cell-mediated immune responses to several antigens were studied in a large group of patients with multiple sclerosis, and in controls. Patients were more likely than controls to have the DRw2 antigen. They had higher mean antibody titers to measles but not to cytomegalovirus, herpes 1, or herpes 2, and had less competent cell-mediated responses. Antibody titers to measles were lower and cell-mediated immune responses were more effective in patients with the DRw2 antigen in patients than in patients without it. This apparent specificity for measles suggests that the etiology of multiple sclerosis is related to the immune response to measles or related viruses.

Constitutional symptoms and health-related quality of life in patients with symptomatic HIV disease.

PURPOSE: To assess the severity of constitutional symptoms in persons with human immunodeficiency virus (HIV) infection, and their relationship to health-related quality of life (HRQOL). PATIENTS AND METHODS: Two hundred five HIV-infected patients (93% male, 26% African American, 28% Latino, 39% white, 7% other ethnicity) with diarrhea, fever, or weight loss were studied at a county hospital and a Veterans Administration hospital in southern California. Consenting subjects were administered a battery that included 11 scales measuring various aspects of health-related quality of life and detailed questions about six constitutional symptoms or symptom complexes (myalgias, exhaustion, anorexia/nausea/vomiting, night sweats, fever, and weight loss) as well as about other manifestations of HIV disease. RESULTS: Constitutional symptoms except weight loss were all strongly related to all measures of quality of life. On 0 (worst) to 100 (best) point scales, mean scores ranged from 34 (for individuals having all five symptoms other than weight loss) to 78 (for those with none) for physical function, 43 to 79 for emotional well-being, and 36 to 73 for social function. Adjustment for helper T-lymphocyte counts, duration of illness, and demographic characteristics did not diminish these associations. CONCLUSION: The presence, number, and severity of constitutional symptoms in HIV disease is strongly related to health-related quality of life in symptomatic HIV-infected individuals. Identifying and treating these very common symptoms has the potential to improve quality of life in these patients.

Similar levels of immune complexes in cases of multiple sclerosis and their unaffected relatives.

To investigate the possible effect of the hypothetical multiple sclerosis susceptibility (MSS) gene on circulating immune complexes, we employed a sensitive assay to test for the presence of immune complexes in sera of MS patients and unaffected relatives classified by the presence/absence of HLA-defined markers for the MSS gene. We found no significant differences between cases and relatives. The results suggest that elevated immune complex levels in MS patients' sera reported by others may not be unique to MS cases, but may represent instead a familial phenomenon. We also report a possible association between the A3 + B7 haplotype and increased immune complexes.

Persistently seronegative men from whom HIV-1 has been isolated are genetically and immunologically distinct.

Studies in both monkeys and humans have suggested that transient infection with HIV-1 can occur without provoking a measurable humoral immune response. The objective of this study was to look for genetic and immunologic correlates of transient HIV-1 infection in antibody-negative men from whom HIV-1 had been isolated. The distributions of MHC class I, class II, and TAP (transporter protein associated with antigen processing) region genes were compared between 23 persistently seronegative men from whom HIV-1 was isolated at least once (isol+/Ab-) and 137 men who seroconverted. A subset of 13 of the 23 isol+/Ab- men were compared to 27 seronegative men for distribution of CD25+CD4+ and CD25+CD8+ cells in the absence of exogenous immunologic stimulation. The prevalences of the TAP1.4, and a combination of TAP1.4, and TAP2.3 variants were significantly higher in the isol+/Ab- men. The proportion of CD8+ cells that expressed CD25+ antigen was also significantly higher in the isol+/Ab- men than in the seronegative men. We conclude that isol+/Ab- men may be genetically and immunologically distinct from HIV-1 susceptible men. We hypothesize that activated CD8+ cells may have cleared HIV-1 infection in these men through genetically mediated influences of the TAP genes on the presentation of peptides by HLA class I molecules.

AIDS onset at high CD4+ cell levels is associated with high HIV load.

To identify factors associated with development of AIDS at high CD4+ cell levels a nested case-control study using data from the Multicenter AIDS Cohort Study (MACS) was conducted. HIV-1-infected men who developed AIDS with > or =300/mm3 CD4+ cells (AIDS men) were compared to men who had > or =300/mm3 of CD4+ cells, but remained AIDS free for at least 2 years. The AIDS men had higher plasma HIV-1 RNA levels (mean 10(5.02) vs. 10(4.42), p<0.01) and neopterin levels (mean 18.3 vs. 11.5 units/ml, p<0.05) before the AIDS diagnosis than did the AIDS-free men. A significantly higher proportion of the AIDS men reported genital herpes within the year prior to their initial AIDS diagnosis than did the AIDS-free men (21.9 vs. 4.4%, p<0.05). The higher viral load at relatively high CD4+ cell levels in men who subsequently developed AIDS within 6 months supports the hypothesis that elevated levels of HIV precede CD4+ decline and are the major factor in determining risk of AIDS even at high levels of CD4+ cell levels.

Predictors of clinical AIDS in young homosexual men in a high-risk area.

One hundred and sixty-seven homosexual men in Los Angeles characterized by HIV antibody, T-cell numbers, titres to cytomegalovirus (CMV), and specific sexual practices were followed for two years for immune changes and for more than three years for development of clinical AIDS. Thirty-five per cent had antibody to HIV at baseline. The mean level of T-helper (Th) cells was significantly lower and of T-suppressor (Ts) cells significantly higher in HIV seropositives than in seronegatives. The annualized incidence of HIV seroconversion was 7%. Eight men developed AIDS, an attack rate of 14% in those with HIV antibody at baseline. A number of observations were made: T-cell alterations, except a transient elevation in Ts cells, were unusual in the absence of HIV antibody; a seropositive man with a T-cell alteration was significantly less likely to revert to 'within normal limits' than was a seronegative man; a steady decline in the number of Th cells preceded onset of clinical AIDS; the number of Ts cells remained higher in men subsequently developing AIDS than in other seropositive men; clinical AIDS occurred only in men with HIV antibody whose CMV antibody levels were above the median for the group (1:1600); and the attack rate for clinical AIDS was 50% in men with HIV antibody and elevated CMV who at baseline had either: fewer than 325 Th cells/cc, or whose Th/Ts ratio was below 0.8 (but whose levels of Th and Ts cells were within normal limits).(ABSTRACT TRUNCATED AT 250 WORDS)