Sirkka-Liisa Valle

Cognitive changes as early signs of HIV infection

ABSTRACT‐ Neuropsychological examination was performed on 13 patients and 10 matched controls to assess the brain involvement of patients with human immunodeficiency virus (HIV) infection. HIV‐infected patients showed a significant decline in visuomotor, visuoconstructive and practical abilities as well as in motorfree visuospatial performance and repeating a long sentence. These findings could not be explained by the concomitant mental depression of these patients. Neither were they associated with any particular stage of HIV infection. The results suggest that mild cognitive changes may be detected even in the early stages of HIV infection, when examined by appropriate neuropsychological methods.

DIVERSITY OF CLINICAL SPECTRUM OF HTLV-III INFECTION

In a prospective follow-up volunteer study lasting 4 to 16 months, 17 of 200 homosexual men living in Finland had antibodies to human T-lymphotrophic virus type III (HTLV-III). 1 man who initially had a low titre of HTLV-III antibodies became seronegative within 6 months without any symptoms developing, and a seronegative man became seropositive. 14 men had high titres of HTLV-III antibodies when they first joined the study and during the study titres rose in all other HTLV-III-positive men except those with AIDS. Initially 9 men were symptom-free, 3 had lymphadenopathy syndrome (LAS), 3 had AIDS-related complex (ARC), and 2 had AIDS. During follow-up LAS developed in 3 symptom-free HTLV-III positive men but none of those with LAS or ARC progressed to AIDS. Most HTLV-III-positive men, including those who were otherwise symptom-free, had mucocutaneous lesions generally associated with immune deficiency. Regardless of the symptoms, those with increasing HTLV-III antibody titres showed lowered T helper/T suppressor ratios, decreased numbers of T helper cells, and/or diminished responses to tuberculin antigen (PPD). These results suggest that the clinical spectrum of HTLV-III infection ranges from transient infection through chronic provirus state, asymptomatic virus producer state, LAS or ARC, and rarely full-blown AIDS. Cofactors probably determine the final outcome of infection in the individual.

Oral candidal infection as a sign of HIV infection in homosexual men

The oral mucosae of 66 homosexual men were examined clinically and by means of cultivation to determine the presence of Candida infection. In addition, clinically detected mucosal changes were recorded and a biopsy specimen was obtained for the histopathologic classification. A total of forty one subjects (62%) showed clinical evidence of candidiasis. Fourteen (21%) of the sixty-six men were seropositive for human immunodeficiency virus (HIV). A total of thirteen of fourteen (93%) of the seropositive men and twenty-six of fifty-two (50%) of the HIV seronegative men had culture-confirmed oral candidiasis. In the latter group, oral candidiasis was clearly correlated to cigarette smoking. Clinical mucosal changes other than candidiasis were found in forty-five of the sixty-six subjects studied. The most frequent finding was trauma resulting from biting, which was usually localized on the cheek. Leukoplakia was found in twelve of sixty-six subjects, while cauliflower-like condylomas were present in 4 persons. The results emphasize the frequent occurrence of different oral lesions in subjects seropositive for HIV and in those at high risk for HIV infection. Oral examination in search for potential early manifestations of HIV infection in homosexual men is advocated.

Dermatologic findings related to human immunodeficiency virus infection in high-risk individuals

A variety of dermatologic disorders have been associated with human immunodeficiency virus (HIV) infection. This prospective study reports the frequency of mucocutaneous findings in 237 individuals at high risk for HIV infection, 33 of whom were HIV seropositive, during a follow-up of 5 to 36 months; 12.1% of the study population, all of them HIV seronegative, were devoid of any pathologic changes of the skin or mucous membranes, whereas all HIV-seropositive individuals exhibited one or several pathologic conditions during the observation period. Oral candidiasis, seborrheic and infectious eczematoid dermatitis, and acquired ichthyosis were among the most frequently encountered dermatologic disorders among the HIV-seropositive individuals, and a worsening of the skin symptoms accompanied the clinical deterioration of the patients.

Cognitive performance in HIV‐1 infection: relationship to severity of disease and brain atrophy

We examined cognitive performance in 72 HIV‐1 infected patients and 34 controls. None of the patients had opportunistic infections or unusual neoplasms of the central nervous system (CNS). Factors other than HIV‐1 known to cause cognitive decline were excluded from both groups. Cognitive functioning analysed with special emphasis on the severity of HIV infection was related to neuroradiological and immunological findings. In patients with AIDS‐related complex (CDC IVa) or AIDS (CDC IVc,d), a deterioration of memory as well as cognitive speed and flexibility was detected. Furthermore, memory deficits were associated with central cerebral and infratentorial atrophy in those patients, while no association was found between cognitive deficits and immunological abnormalities. Patients at CDC stages II or III showed slight association between altered cognitive speed and flexibility and elevated leukocyte count, suggesting a subclinical CNS disease already at early stages of HIV infection.

B-cell epitopes in HIV-1 Tat and Rev proteins colocalize with T-cell epitopes and with functional domains.

We describe the characterization of the B-cell epitopes of HIV-1 regulatory proteins Tat and Rev. The prevalence of antibodies to these proteins among human immunodeficiency virus (HIV)-1-infected individuals was examined by enzyme-linked immunosorbent assay (ELISA) and by Western blotting. The Tat and Rev antibody-positive sera were selected for epitope mapping performed with partially overlapping synthetic peptides bound to polyethylene pins. Eighteen and twelve percent of HIV-infected individuals had antibodies against Tat or Rev, respectively. In Tat, four epitopic regions were identified, situated within amino acids 6-10 (PRLEP), 21-37 (ACTNCYCKKCCFHCQVC), 39-58 (ITKALGISYGRKKRRQRRRA) and 74-82 (TSQSRGDPT). The most frequently recognized epitopic regions were located in the middle of the protein. In Rev, the two most frequently recognized epitopic regions were near the amino terminus of the protein within amino acids 12-20 (LIRTVRLIK) and 38-49 (RRNRRRRWRERQ). A third epitope was mapped around amino acids 55-62 (ISERILGT) and a fourth around amino acids 78-83 (LERLTU). To analyze the specificity of Tat and Rev epitopes, soluble synthetic peptides representing the identified epitopes were used in an ELISA assay, and the recognition of most epitopes was shown to be specific for HIV-1-infected individuals. In addition, many of the Tat and Rev epitopes were shown to overlap with regions having functional activity or with regions previously identified as T-cell epitopes.

CSF and serum β‐2‐microglobulin in HIV infection related to neurological dysfunction

ABSTRACT— Elevated (< 2.2 mg/l) CSF β‐2‐microglobulin (β2m) level was found in 9 of 16 neurologically symptomatic patients but in only 4 of 21 who were neurologically symptom‐free (P < 0.01). Serum β2m concentration was elevated (<2.5 mg/l) in 12 of 16 neurologically symptomatic patients but in only 8 of 21 symptom‐free patients (P < 0.01). When the CSF and serum β2m levels were related to various stages of HIV infection, the highest mean values for both CSF and serum were found in patients with acquired immunodeficiency syndrome (AIDS), followed by lower values in AIDS‐related complex (ARC), lymphadenopathy syndrome (LAS), and asymptomatic seropositive individuals (ASX), in decreasing order of preference. Our results suggest that elevated β2m in CSF and serum is related to the stage of general HIV infection and that elevated CSF β2m in the presence of intact BBB may be useful in evaluating CNS involvement in HIV‐infected patients.

EEG in Early HIV-1 Infection is Characterized by Anterior Dysrhythmicity of Low Maximal Amplitude

We analyzed the EEGs of 67 HIV-1-infected patients at various stages of the disease and of 35 HIV-1-seronegative controls. The most common EEG abnormality in HIV-1 infection was an increased amount of generalized episodic or persistent, predominantly anterior slow activity, associated with a low level of maximal amplitude. When compared to the controls, a lower maximal amplitude of dominant background activity (p less than 0.001), and more marked generalized (p less than 0.01) and anterior (p less than 0.001) disturbances were already seen in early stages of HIV-1 infection. EEG abnormalities were more severe in patients with advanced HIV-1 infection than in those at early infection (p less than 0.001 to p less than 0.05). The presence of a more marked, posteriorly (p less than 0.01) accentuated, generalized slow activity (p = 0.02) was found more often in patients with T-helper cell counts lower than 0.4 x 10(9) (p = 0.05) than in those with higher numbers of T-helper cells. No clear associations were found between the severity of EEG abnormalities and the duration of HIV-1 infection. Our results suggest that EEG is a sensitive method in detecting subclinical functional cerebral disturbances caused by HIV-1.

Serological responses to mycoplasmas in Hiv-infected and non-infected individuals

ObjectiveTo assess the frequency of mycoplasma infections in HIV-antibody-positive and -negative individuals by studying the serological responses against mycoplasmas, especially Mycoplasma fermentans and M. pirum. DesignAn enzyme-linked immunosorbent assay (ELISA) was used to measure immunoglobulin G (IgG) class antibody concentrations against six mycoplasma species in sera of HIV-positive and HIV-negative individuals. MethodsSerum samples were obtained from 30 HIV-positive individuals (10 asymptomatics, 10 with lymphadenopathy syndrome and 10 with AIDS), 10 HIV-negative partners of HIV-positive individuals and 40 HIV-negative blood donors. Antibodies to M. fermentans strains incognitus and PG18, M. pirum, M. genitalium, M. pneumoniae and M. hominis were assessed by immunoblot or ELISA. Absorbance values were taken as a semiquantitative measurement for antibody concentration and an arbitrary cut-off value (0.8) was set to establish seroprevalence. ResultsThere was no significant difference in the mean IgG concentrations of any of the six mycoplasmas between HIV-positive and HIV-negative groups. Antibody concentrations were also similar in different clinical phases of HIV infection. Antibody concentrations to different mycoplasma strains were compared with each other to reveal eventual cross-reactions caused by shared antigens; the strongest correlation (r = 0.836) was found between M. fermentans strains incognitus and M. pirum antibody concentrations. The correlation between M. fermentans strains incognitus and PG18 was also significant but weaker (r = 0.522). No shared antigens between M. fermentans strain incognitus and M. pirum were demonstrated by immunoblot. ConclusionsAntibodies against M. fermentans type strain PG18, strain incognitus and against M. pirum are detected infrequently and their presence does not correlate with HIV infection per se or with the clinical stage of HIV infection.

IMMUNE FUNCTIONS IN HTLV-III ANTIBODY POSITIVE HOMOSEXUAL MEN WITHOUT CLINICAL AIDS

This letter reports data on clinical and immunologic characteristics of 175 homosexual men living in Finland 15 (9%) of whom were anti-human T-lymphotropic virus type III (HTLV-III)-positive. Of the latter 2 had acquired immunodeficiency syndrome (AIDS) 5 had lymphadenopathy syndrome and 2 had enlarged lymph nodes but did not meet the criteria for lymphadenopathy syndrome. 27 homosexuals had a decreased T-helper: T-suppressor ratio characterized in the antibody-positive group by very low absolute T-helper cell counts and in the antibody-negative group by very high T-suppressor cell counts. Clinical and immunologic findings were similar to those in most cases of HTLV-III seropositivity although 1 man with lymphadenopathy-associated syndrome and 1 with symptoms suggestive of pre-AIDS has normal immunologic findings. In addition 2 men with lymphocyte stimulation aberrations became antibody negative and have remained symptom free througout the 10-month study period. During this 10-month follow-up no HTLV-III-antibody negative immunosuppressed man has shown seroconversion or acquired AIDS.