Immune function and neuropsychological performance in HIV-1-infected homosexual men

This study explores the relationship of immune dysfunction to the neuropsychological performance of individuals infected with HIV-1. Fifty-five HIV-positive homosexual men and 37 negative homosexual controls were evaluated using neuropsychological measures, physical exams, and measures of immune functioning. There were no significant differences favoring HIV-negative subjects over HIV-positive subjects. HIV-positive subjects, in fact, performed slightly better on attention and memory procedures. The HIV-positive subjects were then stratified according to the Centers for Disease Control symptom groupings (Group II, asymptomatic, n = 19; Group III, lymphadenopathy, n = 17; and Group IVA or C-2, symptomatic, non-AIDS, (n = 19). There were no significant neuropsychological differences among the three CDC groups. The HIV-positive subjects were also stratified on two measures of immune functioning: absolute CD4 counts (< 200, 201-400, > 400) and beta 2-microglobulin (beta 2M) (> or = 5.0, 3.0-5.0, < 3.0). Individuals with greater immune compromise, as measured by beta 2M, were more impaired on measures of attention and memory and had greater overall neuropsychological impairment (p < 0.05). Furthermore, 57% of the subjects who were abnormal on beta 2M were also impaired on measures of attention and memory, whereas only 14% of those with normal beta 2M were impaired on these same measures (p < 0.05). These results suggest that HIV-positive asymptomatics without evidence of immune compromise do not appear to be at greater risk of cognitive impairment than HIV-negative controls. However, for those HIV-positive individuals who are immune-compromised (even while asymptomatic), there is increased risk of neuropsychological impairment. These results also suggest that knowledge of serostatus and the use of the CDC classification system alone are insufficient in exploring the development of neuropsychiatric changes in HIV-1 infection.     

Kidney morphological changes in relation to long-term renal function and metabolic control in adolescents with IDDM

OBJECTIVE: To investigate the impact of HIV infection on the prevalence, incidence and short-term prognosis of squamous intraepithelial lesions (SIL), in a prospective study with 1-year follow-up. METHODS: Between 1993 and 1995, 271 HIV-positive and 171 HIV-negative women at high risk of HIV infection were recruited, 365 (82.6%) of whom completed the 1-year follow-up. The women underwent a Papanicolaou smear test at inclusion and at 6 and 12 months. Human papillomavirus (HPV) was detected at inclusion by Southern blot and PCR. RESULTS: The SIL prevalence ranged from 7.5% for HIV-negative to 31.3% for HIV-positive women with CD4 cell counts < 500 x 10(6)/l (P < 0.001). Other factors associated independently and significantly with SIL prevalence were HPV-16, 18, 33 and related types, HPV-31, -35, -39 and related types, lifetime number of partners, younger age, past history of SIL and lack of past cervical screening. The SIL incidence ranged from 4.9% in HIV-negative women to 27% in HIV-positive women with CD4 cells < 500 x 10(6)/l (P < 0.001). Progression from low- to high-grade SIL during follow-up was detected in 38.1% of HIV-positive women with CD4 cells < or = 500 x 10(6)/l but in no HIV-negative nor HIV-positive women with CD4 cells > 500 x 10(6)/l. HPV-16, 18, 33 and related types were also associated with higher incidence of SIL and progression from low- to high-grade SIL. CONCLUSION: HIV-induced immunodeficiency is associated with high prevalence, incidence and persistence/progression of SIL. A pejorative influence of HIV infection without marked immunodeficiency is less clear. HIV-positive women with SIL may thus benefit from early treatment when a useful immune response is still present.     

Production of androgenetic haploids in zebrafish with ultraviolet light

Anal cancer is more commonly found in homosexual and bisexual men than cervical cancer is in women. Invasive anal cancer may be preceded by anal squamous intraepithelial lesions (ASIL), and treatment of ASIL may prevent the development of anal cancer. We characterized the prevalence and risk factors for ASIL in 346 HIV-positive and 262 HIV-negative homosexual men. Anal cytology, biopsy of visible anal lesions, and human papillomavirus (HPV) tests were performed, and data on HIV serostatus, CD4 count, and medical and lifestyle history were collected. ASIL was diagnosed in 36% of HIV-positive men and 7% of HIV-negative men (relative risk [RR] = 5.7; 95% confidence interval [CI], 3.6-8.9). Among HIV-positive men, the RR for ASIL increased with lower CD4 levels but was elevated even in men with CD4 levels >500/mm3 (RR = 3.8; 95% CI, 2.1-6.7) when compared with HIV-negative men. High-level HPV infection, as measured by detection of both hybrid capture (HC) group A and group B types, was another significant risk factor for ASIL in both HIV-positive men (RR = 8.8; 95% CI, 2.3-35) and HIV-negative men (RR = 20; 95% CI, 5.5-71) when compared with HC-negative men. HIV-negative men with anal HPV infection and HIV-positive men, regardless of CD4 level, are at high risk for ASIL.     

Neurophysiological parameters and CD4 lymphocyte count in patients infected by human immunodeficiency virus

INTRODUCTION AND OBJECTIVE: The human immunodeficiency virus (HIV) causes serious, irreversible, progressive deterioration of the immune and nervous systems. The main target cells are the 'helper' T lymphocytes and monocyte-macrophage cells with CD4 molecules on the surface acting as virus receptors. In this study we attempt to find whether the immune state and the nervous system are involved in parallel, or whether, on the contrary, HIV neurotropism is such that it leads to early nerve involvement, out of proportion to that of the immune system. PATIENTS AND METHODS: We studied a total of 66 persons, 30 seronegative and 36 seropositive, with different CD4 lymphocyte counts. In all cases motor and sensory conduction studies were done in the arms and legs, namely auditory, visual and somatosensory evoked potentials and also endogenous potentials (mainly P300). CONCLUSIONS: There are neurophysiological parameters which give pathological figures, even when immunity is maintained (figures of CD4 greater than 500/mm3) especially with regard to the figures for sensitivity of the legs, somatosensory evoked potentials and P300. Moreover, these are increased and others added at the same time as the CD4 count falls as the disease advances.     

Determination of 7alpha-hydroxycholesterol in dog plasma by high-performance liquid chromatography with fluorescence detection

One of the groups at highest risk of anal cancer is homosexual and bisexual men. Like cervical cancer, anal cancer is associated with human papillomavirus (HPV) infection. Anal HPV infection was characterized in a study of 346 human immunodeficiency virus (HIV)-positive and 262 HIV-negative homosexual and bisexual men. Anal HPV DNA was detected in 93% of HIV-positive and 61% of HIV-negative men by polymerase chain reaction. The spectrum of HPV types was similar in HIV-positive and HIV-negative men, with HPV-16 the most common type. Infection with multiple HPV types was found in 73% of HIV-positive and 23% of HIV-negative men. Among HIV-positive men who were positive by hybrid capture for group B HPV types (16/18/31/33/35/39/45/51/52/56/58) or group A types (6/11/42/43/44), lower CD4 cell levels were associated with higher levels of group B DNA (P = .004) but not group A DNA. These data suggest increased replication of the more oncogenic HPV types with more advanced immunosuppression.     

Depressed mood does not explain neuropsychological deficits in HIV-infected persons.

The relationship of depressed mood to cognitive disturbance in HIV infection was examined in a sample of 139 homosexual men. Ss were grouped according to the classification of the Centers for Disease Control: 39 were in Group IV, 62 were in Group II or Group III, and 38 were HIV-negative. Ss completed the Profile of Mood States and 10 neuropsychological tests. Analysis employing a classification approach indicated that, although symptoms of depression and neuropsychological impairment were more common in Ss who were HIV-positive, particularly those classified as Group IV, there were no systematic relationships between depression and neuropsychological impairment. Depressed mood and cognitive disturbance each seem to have unique associations to HIV illness status. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sexual transmission and the natural history of human herpesvirus 8 infection

BACKGROUND: Although human herpesvirus 8 (HHV-8) has been suspected to be the etiologic agent of Kaposi's sarcoma, little is known about its seroprevalence in the population, its modes of transmission, and its natural history. METHODS: The San Francisco Men's Health Study, begun in 1984, is a study of a population-based sample of men in an area with a high incidence of human immunodeficiency virus (HIV) infection. We studied all 400 men infected at base line with HIV and a sample of 400 uninfected men. Base-line serum samples were assayed for antibodies to HHV-8 latency-associated nuclear antigen (anti-LANA). In addition to the seroprevalence and risk factors for anti-LANA seropositivity, we analyzed the time to the development of Kaposi's sarcoma. RESULTS: Anti-LANA antibodies were found in 223 of 593 men (37.6 percent) who reported any homosexual activity in the previous five years and in none of 195 exclusively heterosexual men. Anti-LANA seropositivity correlated with a history of sexually transmitted diseases and had a linear association with the number of male sexual-intercourse partners. Among the men who were infected with both HIV and HHV-8 at base line, the 10-year probability of Kaposi's sarcoma was 49.6 percent. Base-line anti-LANA seropositivity preceded and was independently associated with subsequent Kaposi's sarcoma, even after adjustment for CD4 cell counts and the number of homosexual partners. CONCLUSIONS: The prevalence of HHV-8 infection is high among homosexual men, correlates with the number of homosexual partners, and is temporally and independently associated with Kaposi's sarcoma. These observations are further evidence that HHV-8 has an etiologic role in Kaposi's sarcoma and is sexually transmitted among men.     

HIV sexual risk behavior following bereavement in gay men.

The present study followed a group of 100 gay men up to 1 year before and 1 year after losing a partner to AIDS (University of California, San Francisco Coping Project). Following bereavement, participants were at increased risk for engaging in unprotected anal intercourse: at 4 to 6 months for HIV-negative men and at 8 to 12 months for HIV-positive men. Sociodemographic variables, HIV serostatus, substance use, depression, prebereavement relationship quality, and social support did not explain sexual risk-taking in this sample. However; men who engaged in unprotected anal intercourse were twice as likely to be involved in a new primary relationship as those who did not. The authors concluded that risk varies over time by HIV status and may involve engagement in new relationships. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Evaluating outcome after spinal cord injury: what determines success? 1996 Donald Munro Lecture

OBJECTIVE: To determine the nature and extent of cognitive deficits in early stage (asymptomatic) human immunodeficiency virus (HIV)-positive homosexual and bisexual men. DESIGN: A cross-sectional design was used to compare 27 HIV-positive, asymptomatic (Centers for Disease Control and Prevention stages 2 and 3) homosexual and bisexual men, who were designated as the seropositive group, with 29 seronegative homosexual and bisexual men, who were designated as the control group. METHODS: The participant groups were closely matched on a number of demographic and lifestyle variables. Participants were carefully and repeatedly screened for substance abuse, a history of psychiatric problems, use of psychoactive medications, and neurological problems. All participants completed an extensive neuropsychological battery and a computerized information processing battery to identify cognitive deficits. RESULTS: No significant between-group differences were found on either the neuropsychological assessments or the information processing tests. Additionally, we found no evidence of a subgroup of seropositive, asymptomatic individuals with general cognitive slowing. CONCLUSIONS: Educated, HIV-positive asymptomatic individuals may show little difference in cognitive performance compared with a group of matched controls when the groups are carefully screened and matched. Additionally, computerized tests may be no more sensitive than neuropsychological tests to cognitive decrements for these types of participants.     

Lymphoproliferative immune function in the Sydney Blood Bank Cohort, infected with natural nef/long terminal repeat mutants, and in other long-term survivors of transfusion-acquired HIV-1 infection

OBJECTIVES: To assess T-helper cell immune function (proliferation) in members of the Sydney Blood Bank Cohort (SBBC) compared with other individuals with transfusion- and sexually acquired HIV-1 infection and with matched HIV-negative controls. DESIGN AND METHODS: Decreasing CD4 counts and T-helper cell function are associated with disease progression. Peripheral blood mononuclear cells (PBMC) from study subjects were assayed for in vitro proliferative responses to HIV-1-derived antigens, recall antigens and alloantigen. T-helper cell function and CD4 counts in members of the SBBC were followed longitudinally. RESULTS: Proliferative responses and CD4 counts from members of the SBBC were similar to or better than those of other transfusion- or sexually-acquired HIV-1-positive long-term non-progressors (LTNP), including the HIV-negative matched SBBC control groups. However, individuals with disease progression had reduced or undetectable proliferative responses to recall antigens but a conserved response to alloantigen; they also had low CD4 counts and low CD4:CD8 ratios. In the SBBC, these immune parameters were usually stable over time. CONCLUSIONS: The unique SBBC with natural nef/long terminal repeat deletions in the HIV-1 genome were genuine LTNP without showing signs of disease progression. They appeared to be a group distinct from the tail-end of the normal distribution of disease progression rates, and may remain asymptomatic indefinitely. The SBBC virus may form the basis of a live attenuated immunotherapeutic or immunoprophylactic HIV vaccine.     

Comparison among delayed-type skin tests, serum IgE levels and peripheral blood CD4 in HIV-positive patients

Three groups of HIV-positive men and a control group of healthy subjects were evaluated simultaneously by delayed-type skin tests with recall antigens detection of CD4 cell counts in peripheral blood and the IgE serum levels. Delayed-type skin test reactivity and CD4 cell counts in peripheral blood decreased while IgE serum levels increased as immune imbalance progressed with the worsening of HIV infection (p = 0.003 between controls and HIV-positive patients). The existence of atopy did not significantly influence IgE serum levels in the groups of HIV-positive patients (p < 0.2). Candidin appeared as a useful antigen in the delayed-type skin tests considering that it was the only antigen that remained positive with low values of CD4 cell counts (< or = 250/mm3). The detection of serum IgE levels as well as the performance of delayed-type skin tests with recall antigens are useful tools to evaluate immunological status whereas the number of CD4 in peripheral blood is critical for determining the initiation of antiretroviral therapy.     

Effect of human immunodeficiency virus on hepatitis C virus infection among injecting drug users

To assess the effect of human immunodeficiency virus (HIV) immunosuppression on ongoing hepatitis C virus (HCV) infection, CD4 lymphocyte counts and serum concentrations of HCV RNA, HIV RNA, and alanine aminotransferase (ALT) were evaluated among members of a cohort of injecting drug users (IDUs). With 100 participants randomly selected at various stages of HIV-related immunosuppression, serum HCV RNA concentrations increased with age (P = .007) and were higher in HIV-positive IDUs with 201-500 (P = .026) and 51-200 (P = .004) CD4 cells/mL than in HIV-negative participants. Among 27 HCV-infected IDUs who acquired HIV infection, serum HCV RNA concentrations varied between semiannual visits by a mean of 0.45 logs, increasing by 0.60 logs after HIV seroconversion (P < .0001), by 0.12 logs each subsequent year (P = .006), and by 0.36 logs per log increase in CD4 cells (P = .01). Serum ALT levels were similar between HIV-positive (40.1 IU/mL) and HIV-negative (45.4 IU/mL) patients (P > .10). While HIV infection and possibly HIV progression are associated with increased HCV RNA levels, other factors appear to affect biochemical and virologic markers of HCV infection in some dually infected persons.     

High-risk sexual behavior and knowledge of HIV antibody status in the San Francisco City Clinic Cohort.

Evaluated the effectiveness of human immunodeficiency virus (HIV) testing and counseling among homosexual and bisexual men participating in the San Francisco City Clinic Cohort (Centers for Disease Control, 1987). Behavioral data from 181 men who learned their HIV antibody status between 1985 and 1987 were compared with data from 128 men who were tested but declined to receive their results. Significant declines in risk indices for unprotected receptive and insertive anal intercourse occurred between 1983–1984 and 1986–1987, but these declines were independent of both knowledge of HIV status and actual serostatus. Ss who chose to learn their HIV status were no more likely to report depression or anxiety subsequent to testing. Frequent access to and discussion of risk-reduction information may be important motivators of behavioral change. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Techniques, coils, pulse sequences, and contrast enhancement in pediatric musculoskeletal MR imaging

OBJECTIVE: This study aimed to investigate rates of psychiatric disorder in human immunodeficiency virus (HIV) infection, in an Australian sample of homosexual and bisexual men. METHOD: A cross-sectional study of a total of 65 HIV sero-negative (HIV-) and 164 HIV sero-positive men (HIV+) (79 CDC stage II/III and 85 CDC stage IV) was conducted in three centres. Lifetime and current prevalence rates of psychiatric disorder were evaluated using the Diagnostic Interview Schedule Version IIIR (DIS-IIIR). RESULTS: Elevated current and lifetime rates of major depression were detected in both HIV negative and HIV positive homosexual/bisexual men. Lifetime rates of alcohol abuse/dependence were significantly elevated in HIV positive men (CDC group IV) when compared with HIV negative men. Among the HIV positive group the majority of psychiatric disorders detected were preceded by a pre-HIV diagnosis of psychiatric disorder. Major depression represented the disorder most likely to have first onset after HIV infection diagnosis. CONCLUSIONS: Lifetime rates of major depression were elevated in this sample of HIV-negative and HIV-positive men. In the HIV-positive men, psychiatric disorder was significantly associated with the presence of lifetime psychiatric disorder prior to HIV infection diagnosis. The findings indicate the importance of evaluation of psychiatric history prior to HIV infection and the clinical significance of depressive syndromes in this population.     

HIV infection affects parietal-dependent spatial cognition: Evidence from mental rotation and hierarchical pattern perception.

Human immunodeficiency virus (HIV) in the asymptomatic phase of the infection impairs some aspects of cognition, but little is known about how visuospatial functions are affected. In the present study, performance on tasks of mental rotation and hierarchical pattern perception was investigated in 14 HIV-positive men and 12 age- and education-matched HIV-negative men. Processes related to mental rotation of objects and hands were impaired in HIV-positive participants as compared to the HIV-negative group. The HIV-positive group was also impaired on hierarchical pattern perception of local targets under global biasing conditions. Consistent with these results, the HIV-positive participants showed impaired performance on standard clinical neuropsychological tests of visuospatial function. These findings indicate that the detrimental effects of HIV on cognition appear even in asymptomatic individuals and affect diverse visuospatial functions that depend upon the integrity of parietal brain regions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The renal medullary thick ascending limb as a model for understanding lipid mediators in sepsis

OBJECTIVE: To evaluate the impact of HIV illness on psychiatric and psychosocial functioning over 3 years in a sample of male and female HIV-positive injecting drug users (IDU), with a comparison group of HIV-negative male and female IDU. DESIGN: As part of a multidisciplinary study, 121 men (69 HIV-positive, 52 HIV-negative) and 66 women (36 HIV-positive, 30 HIV-negative) were evaluated semiannually for seven visits. Attrition, unrelated to sex or serostatus, was 33%. RESULTS: At baseline, rates of major depression and dysthymia ranged from 15% (HIV-negative men) to 33% (HIV-positive men and HIV-negative women). Global impairment was in the range found in psychiatric patients (mean Global Assessment of Functioning scores, 46-51). Higher levels of social support and less social conflict were independently associated with decreased distress and improved global functioning among both men and women. For both HIV-positive groups, degree of improvement over time was related to degree to HIV progression: those who remained healthier in terms of CD4 count and illness stage showed more improvement. HIV-seronegative status was associated with less distress for men but not for women. Overall, women reported higher levels of psychiatric distress than men. CONCLUSIONS: High rates of psychopathology were found in this IDU cohort, independent of HIV status and sex. Although rates of psychopathology, injecting drug use and distress declined slightly during the study, they remained elevated; accordingly, psychiatric services are indicated for this population.     

Congenital bronchoesophageal fistula in an adult

The seroprevalence of human herpesvirus 8 (HHV-8) in the Swiss population was investigated. By enzyme-linked immunosorbent assay, sera reactive to the recombinant HHV-8 antigen orf 65.2 were found in 24% of human immunodeficiency virus (HIV)-positive patients without and in 92% of HIV-positive patients with Kaposi's sarcoma. Surprisingly, 20% of homosexual HIV-negative men, versus only 7% of heterosexual HIV-negative individuals and 5% of blood donors, had antibodies to HHV-8.     

Anal and penile condylomas in HIV-negative and HIV-positive men: clinical, histological and virological characteristics correlated to therapeutic outcome

Clinical, histological and HPV DNA hybridization findings were analyzed for 73 homosexual and 38 heterosexual men attending for anal warts; therapy results were evaluated retrospectively for 76 of these patients. Concurrent anal and penile warts occurred most commonly in the heterosexual men (p < 0.001). While perianal warts were most common in heterosexuals (p < 0.05), intraanal warts were most common in homosexuals (p < 0.001). Altogether 23 homosexual men were HIV-infected; 13 HIV-positive men followed regarding therapeutic outcome were immunologically relatively intact with mean CD4 counts of 524/mm3. Of 136 biopsy specimens 70% revealed benign hyperplasia, 27% AIN I, 2% AIN II and none AIN III. Of ISH positive samples 94% contained HPV 6/11 and 6% HPV 16/18/31/33. Anal warts were cured after an average of 2.5 (mean 1-10) therapy sessions in 64% of heterosexual, in 84% of HIV-negative homosexual and in 62% of HIV-positive homosexual men. The mean number of therapy sessions against anal warts was highest (p < 0.001) and the time for accomplishing cure for anal and penile warts was longest (p < 0.001) in the heterosexual study group.     

Multiple recurrences of cervical intraepithelial neoplasia in women with the human immunodeficiency virus

OBJECTIVE: To evaluate the long-term outcomes after treatment of cervical intraepithelial neoplasia (CIN) in women infected with the human immunodeficiency virus (HIV). METHODS: Human immunodeficiency virus-infected and HIV-negative women treated for CIN by ablation or excision were followed-up prospectively by cytology and colposcopy for periods of up to 73 months. RESULTS: Among 127 HIV-infected CIN patients, 62% developed recurrent CIN by 36 months after treatment, compared with 18% of the 193 HIV-negative CIN patients. Recurrence rates reached 87% in 41 HIV-infected women with CD4 counts less than 200 cells/mm3. Progression to higher-grade neoplasia, including one invasive cancer, occurred by 36 months in 25% of HIV-infected and 2% of HIV-negative women. After adjusting for age, CIN severity, and treatment type, predictors of recurrence included HIV infection (rate ratio 4.4), and, in HIV-positive women, low CD4 count (rate ratio 2.2). In patients treated by excision, predictors of recurrence included HIV infection (rate ratio 2.0) and residual CIN after treatment (rate ratio 2.7). After a second treatment,a second CIN recurrence developed in 14 of 33 HIV-infected and in one of 17 HIV-negative women. After a third treatment, three of six HIV-infected women developed a third recurrence. With long-term follow-up, 45% of treated HIV-infected CIN patients had chronic condylomatous changes in the cervix compared with 5% of HIV-negative women. CONCLUSION: In HIV-infected women, CIN may recur despite multiple treatments, and chronic condylomatous changes are common. Innovative therapies for controlling CIN in HIV-infected women are needed.     

Electrocardiographic changes in stroke patients without primary heart disease

OBJECTIVE: To examine the HIV seroconversion rate, risk factors for seroconversion, and changes in risk behavior over time in intravenous drug users (IVDU) in San Francisco, 1985-1990. DESIGN: Observational study. SETTING: All methadone maintenance and 21-day methadone detoxification programs in San Francisco. PARTICIPANTS: A total of 2351 heterosexual IVDU, of whom 681 were seronegative at first visit and seen at least twice ('repeaters'). MAIN OUTCOME MEASURES: HIV seroconversion rates, risk factors for seroconversion, and changes in behavior. RESULTS: The HIV seroconversion rate in repeaters was 1.9% per person-year (ppy) of follow-up [2.1% in women versus 1.7% in men (not significant); 4% in African Americans versus 1% in whites (P = 0.006); 3.9% ppy in the first third of the study, 1.2% in the second (P = 0.007), and 1.9% in the last (not significant)]. Risk factors for seroconversion were five or more sexual partners per year [hazard ratio (HR) = 2.6; P = 0.02], use of shooting gallery ever (HR = 2.9; P = 0.02), and less than 1 year (lifetime) in methadone maintenance (HR = 2.7; P = 0.02). Self-reported intravenous cocaine use fell from 33 to 15% over 5 years, shooting gallery use fell from 19 to 6%, and the proportion with five or more sexual partners fell from 25 to 10%. Bleach use rose to 75% of needle-sharers. CONCLUSIONS: The 1985-1990 HIV seroconversion rate in IVDU (1.9% ppy) was comparable to that in San Francisco cohorts of homosexual men (1.4% ppy). A decline in HIV seroconversion coincided with changes in risk behavior. Stable attendance of methadone maintenance was highly protective: the seroconversion rate in subjects with 1 year or more in methadone was 12% ppy.