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Biomedical subjects

E Sandström

Publications and source records attributed to E Sandström.

At least 55 records · Page 3Linked to original sources

High frequency of sexually transmitted diseases among pregnant women in Dar es Salaam, Tanzania: need for intervention.

In order to determine the prevalence and characteristics of sexually transmitted diseases (STDs) in pregnant women (PW) attending a primary health care antenatal clinic (ANC) in metropolitan Dar es Salaam, Tanzania, a randomly selected sample of PW in their second or third trimesters were invited to participate at their first visit. They were interviewed using a questionnaire and underwent genital examination. Genital swabs were obtained for microscopy and/or culture isolation of Candida albicans, Trichomonas vaginalis, and Neisseria gonorrhoeae. Blood specimens were also obtained for serological testing for syphilis and for antibodies to the human immunodeficiency virus (HIV). A total of 777 PW aged 14 to 40 years were seen. Parities ranged from 0 to 10. Prevalence of syphilis, trichomoniasis, gonorrhoea and HIV infection were 4.0%, 22.7%, 3.6% and 15.2%, respectively. At least one acute STD (excluding HIV infection) was found in 32.8% of the PW. The prevalence of multiple STDs (excluding HIV infection) was higher in teenagers (45.3%, 77/170) than in PW in other age groups (29.2%, 177/607) (p < 0.001). The prevalence of HIV infection in teenage PW was 10.0%. Most STDs were least prevalent in PW who were married monogamously. Of the 732 PW who had one or more genital infections (including infection with Candida species), 669 (91.4%) had one or more genital complaints. However, most of the genital complaints were not disease specific. Since this study has shown that the prevalences of acute STDs were high in PW, especially in teenagers, it is recommended that all PW in Tanzania should be screened for STDs syndromically including the use of appropriate clinical and laboratory examination whenever possible.

Adolescent↗

CMV PCR in leucocytes as an early marker for the development of CMV disease in AIDS patients.

The relationship between cytomegalovirus (CMV) DNA in leucocytes and CMV disease in AIDS patients was sought. In 195 HIV-1 infected, mostly AIDS patients, CMV nPCR was performed in 477 peripheral EDTA blood samples which were collected also for CD4 cell counts (403), classic (410) and rapid virus isolation (270), and antigenemia tests (190). Most patients who died were autopsied. Immunohistopathology for CMV was performed. The first 43 patients were classified clinically according to having (A) verified organ involvement of CMV (15), (B) suspected CMV disease due to symptoms (4), or no CMV-associated disease (24). CMV-DNA was detected in the majority of samples (66%) and patients (68%). In contrast, CMV in the samples was detected in only 16% by classical and 11% by rapid isolation and in 8.4% by the antigenemia test. Acquisition of CMV DNA in leucocytes became more common as the CD4 cell counts fell. Detection of CMV DNA was significantly associated with CMV-associated symptoms and later mortality. In conclusion, CMV PCR of DNA in leucocytes is a sensitive and early marker of CMV disease in HIV-infected AIDS patients. It might be a marker to be added to CD4 cell counts for initiation of preemptive therapy.

AIDS-Related Opportunistic Infections↗

[Controlled, clinical trial of isoprinosine administration to HIV-infected patients. Results of a Danish/Swedish multicenter study. The Scandinavian Isoprinosine Study Group].

The safety and efficacy of isoprinosine in HIV-infected individuals were assessed in a multicentre, randomized, double-blind, 24-week study phase, followed by an optional 24-week open treatment phase. The results of the double-blind phase have been reported separately. Of 866 HIV-seropositive individuals randomized, 832 were eligible for efficacy analysis. On completion of the double-blind phase, 596 patients started open treatment. All patients were evaluated with regard to progression to AIDS. Within 48 weeks, 10/412 patients (2.4%) assigned isoprinosine and 27/420 (6.4%) assigned placebo progressed to AIDS (p = 0.005; odds ratio: 2.8, 95% CI: 1.3-6.2). Intention-to-treat analysis showed identical results. No severe adverse reactions or toxicities were observed. We conclude that HIV-infected individuals without AIDS may be safely and effectively treated with isoprinosine.

Acquired Immunodeficiency Syndrome↗

Surgical treatment of cytomegalovirus enterocolitis in severe human immunodeficiency virus infection. Report of eight cases.

PURPOSE: The aim of this study was to describe our experiences of surgical removal of inflamed bowel in cytomegalovirus enterocolitis. METHODS: Eight homosexual males with a mean age of 41 years (range, 29-59 years) and a mean CD4 count of 21 x 10(6)/l (1-60 x 10(6)/l) with advanced human immunodeficiency virus infection and severe cytomegalovirus enterocolitis were treated with ileocecal resection (4 patients) or right-sided hemicolectomy (4 patients). Symptoms were lower abdominal pain, severe diarrhea, fever, and weight loss, unrelieved by anticytomegalovirus therapy. Radiologic examination showed that ulcerative inflammation was limited to the right colon and terminal ileum. Microscopic examination confirmed the cytomegalovirus enterocolitis. Intermittent cytomegalovirus treatment, usually with foscarnet for 10 to 14 days every 4 to 6 weeks was given postoperatively. RESULTS: Two minor postoperative complications occurred: a lesser wound infection and a moderate bleeding from the abdominal wound edges. One patient died after three weeks because of gastrointestinal bleeding from an ulcerating Kaposi's sarcoma lesion and another patient died from unrelated causes three weeks after discharge from the hospital. The remaining 6 patients experienced complete or partial palliation of the abdominal symptoms for a mean of 14 months (range, 5-35 months) until death or the end of observation time. One patient is still alive two years after the operation. The overall mean survival was 12 months (range, 0.5-35 months). Recurrent or persistent symptoms and/or signs of cytomegalovirus enterocolitis occurred in four patients after a mean of seven months. CONCLUSION: Resection of inflamed bowel combined with postoperative anticytomegalovirus treatment leads to excellent palliation and a relatively favorable survival in AIDS patients with cytomegalovirus enterocolitis.

Acquired Immunodeficiency Syndrome↗

Autoreactivity in HIV-infected individuals does not increase during vaccination with envelope rgp160.

The HIV-1 envelope protein contains several regions with amino acid homology to HLA class I and class II molecules. We evaluated possible changes in antibody responses to those regions during vaccination with rgp 160 produced in a baculovirus system. Forty asymptomatic HIV-infected patients with CD4 cell counts above 400 were vaccinated with rgp 160. Twenty-one patients were tissue-typed as HLA A2. Sixty-two percent of these patients exhibited cytotoxic lymphocyte antibodies directed to CD8+, HLA A2 cells. This cytotoxicity decreased during HIV gp160 vaccination. In order to further characterize the specificity of these responses, analogues of HLA class I and HLA-DR peptides were chemically synthesized together with their correct HIV-1 gp160 sequences. Enzyme-linked immunosorbent assays (ELISA) with sera from before, during and after immunization were performed with HIV proteins, peptides and their homologues. All patients showed an increase in their previously poor specific T-cell activation to gp160. Fourteen patients developed increased avidities or titres to HIV proteins and/or peptides. Contrarily, serum IgG titers to the HLA homologous peptides were initially low and decreased further during the course of vaccination. This decrease occurred in the majority of patients, 35-40 of the 40 individuals, depending on the antigen. Independent measures of autoantibodies to Ro/SS-A and La/SS-B remained undetectable.

AIDS Vaccines↗

Presence of autologous neutralizing antibodies against cytomegalovirus (CMV) in serum of human immunodeficiency virus type 1-infected patients shedding CMV in saliva.

This study evaluated whether cytomegalovirus (CMV) neutralizing capacity affected shedding of CMV in saliva in human immunodeficiency virus type 1 (HIV-1)-infected patients and mapped specific epitope reactivity of CMV IgG antibodies. Total CMV IgG titers were significantly higher in symptomatic than in asymptomatic HIV-1-infected patients or controls. All CMV-seropositive patients had neutralizing antibodies to CMV. Shedding of CMV in the saliva of AIDS patients occurs despite the presence of serum antibodies with a high capacity to neutralize autologous CMV isolates. The highest IgG reactivity against a CMV envelope protein (gp116), represented by a peptide, was found in patients with advanced HIV disease. In contrast, identical IgG reactivities against a peptide representing the CMV matrix protein were observed in healthy controls and HIV-1-infected persons.

Adult↗

MT-2 cell tropism of human immunodeficiency virus type 1 isolates as a marker for response to treatment and development of drug resistance.

The correlation of the tropism of human immunodeficiency virus type 1 (HIV-1) isolates for MT-2 cells with response to zidovudine and didanosine treatment and with development of drug resistance was studied. Patients with MT-2-negative but not MT-2-positive HIV-1 had a significant increase in CD4+ lymphocyte counts during the first 6 months of treatment. In both groups and for both drugs, the rate of CD4+ lymphocyte decline decreased after the start of treatment. MT-2-positive isolates were more likely than MT-2-negative isolates to show reduced sensitivity to zidovudine and didanosine. Because the differences in zidovudine sensitivity were first evident after 12 months of treatment, drug resistance was probably not the cause of poor response early in zidovudine treatment in patients with MT-2-positive HIV-1. Thus, patients with MT-2-positive virus have limited benefit from treatment with single nucleoside analogues. Knowledge of MT-2 cell tropism may be important in clinical trials and for choosing treatments for patients.

Adult↗

Zidovudine twice daily in asymptomatic subjects with HIV infection and a high risk of progression to AIDS: a randomized, double-blind placebo-controlled study. The European-Australian Collaborative Group (Study 017)

OBJECTIVE: To evaluate the efficacy of zidovudine given twice daily in subjects with asymptomatic HIV-1 infection and a high risk of progression to AIDS. DESIGN: Randomized, double-blind placebo-controlled trial. SETTING: Multicentre study in five European countries and Australia. PATIENTS: Asymptomatic subjects (n = 329) with CD4 cell counts between 200 and 400 x 10(6)/l, or if > 400 x 10(6)/l, subjects with HIV p24 antigenaemia (> 10 pg/ml). INTERVENTION: Patients were randomly assigned to receive zidovudine 500 mg or placebo twice daily for 104 weeks, following a 250 mg four times daily dose regimen for the first 4 weeks. MAIN OUTCOME MEASURES: The primary end-point was the development of AIDS or severe AIDS-related complex (ARC). Before unblinding the study other end-points were defined: the development of Centers for Disease Control and Prevention (CDC) group IV disease (AIDS, severe ARC and other CDC stage IV disease) and the development of symptomatic HIV disease (AIDS, severe ARC, other CDC stage IV disease and minor HIV disease). Changes in CD4+ cell counts, p24 antigenaemia and toxicity were also reviewed. RESULTS: Median treatment duration was 57 weeks for the placebo and 60 weeks for the zidovudine group, respectively. Progression to AIDS or severe ARC occurred in 17 placebo and 12 zidovudine recipients (log-rank P = 0.26). However, in the first of the 2 study years the rate of progression to AIDS or severe ARC was significantly higher in the placebo than in the zidovudine group. Zidovudine delayed progression to symptomatic HIV disease (P = 0.01); a trend in a delay in progression to CDC stage IV disease was observed (P = 0.08). Zidovudine recipients maintained CD4+ cell counts at or above baseline levels for longer than placebo recipients (P = 0.04). HIV p24-antigen levels decreased in the zidovudine group and returned to pretreatment levels by week 36. Substantial toxicity was not observed. CONCLUSIONS: Zidovudine twice daily is effective in delaying progression to symptomatic HIV disease in high-risk, asymptomatic HIV-infected subjects. Modified definitions of clinical end-points may be useful for evaluating Phase III trials in comparable patient groups in the light of changes in the definition of AIDS and the increasing use of primary prophylaxis against opportunistic infections.

AIDS-Related Complex↗

MT-2 cell tropism as prognostic marker for disease progression in human immunodeficiency virus type 1 infection.

The ability of human immunodeficiency virus type 1 (HIV-1) isolates to replicate in MT-2 cells was investigated as a prognostic marker for disease progression and CD4+ lymphocyte depletion in 53 HIV-1-infected, asymptomatic individuals. MT-2-negative viruses were isolated from 49% of the patients both early and late during the follow-up period; 38% converted from being MT-2 negative to MT-2 positive, while 11% were MT-2 positive throughout the study. One individual showed a fluctuating virus phenotype. The loss of CD4+ lymphocytes was significantly more rapid in MT-2-positive patients. We found a broad spectrum of CD4+ lymphocyte changes in patients whose virus changed its MT-2 tropism. Our data suggest that the changes could be divided into three general patterns. A stable or slowly decreasing CD4+ lymphocyte count changed into a more rapid fall in 44% of the patients, no significant change in rate of decline could be noted in 44% of the patients, while a stable CD4+ lymphocyte level after a change in MT-2 tropism was noted in 12% of the patients. A correlation between MT-2 tropism and clinical symptoms was also noted. Half of the patients with MT-2-negative virus throughout the study were still asymptomatic after a mean follow-up time of 80 months, while only 15% of those who converted remained asymptomatic. All patients with MT-2-positive viruses at the time of inclusion in the study developed HIV-1-related symptoms, and half of them died during the study. The MT-2 status of 16 patients, could be determined at the time of AIDS diagnosis; 50% were Mt-2 positive, while 50% were MT-2 negative. No difference in AIDS-defining diagnoses or CD4+ lymphocyte counts at the time of diagnosis was noted. Knowledge of the HIV-1 phenotype may improve the early recognition of progressive disease.

Adult↗

Immunological and virological interactions in patients receiving passive immunotherapy with HIV-1 neutralizing monoclonal antibodies.

Mouse monoclonal antibodies with high human immunodeficiency virus type 1 (HIV-1) neutralizing titers were used for passive immunotherapy of eleven late-state HIV-infected patients. In five patients the serum level of the core protein p24 decreased, while in five cases it remained unchanged. The level of viral RNA in plasma as measured by quantitative polymerase chain reaction (PCR) decreased in four cases, was stable in another four, and increased in three cases. An anti-mouse (HAMA) response developed in eight patients and anti-idiotypic antibodies appeared in six. Immune complexes that formed in patient sera during the treatment were shown to contain mostly envelope glycoprotein gp120 which decreased in nine of the eleven treated patients toward the end of treatment. Antibodies inhibiting gp120 binding to CD4 became detectable or increased in six patients during immunotherapy. Serology of the HIV-1 V3 region was studied for both the HIV-1 IIIB and MN strains with no or very small changes in titer or avidity after treatment. No change in neutralizing titers to strain HTLVIIIB was observed in serum samples collected before and after treatment was terminated. In nine of the eleven patients stimulation of the T lymphocytes to proliferate in vitro when activated by phytohemagglutinin (PHA) was shown to be increased compared to before treatment. Increased T-cell proliferation was also noted with several antigens such as HIV-1 recombinant antigens, cytomegalovirus (CMV), tetanus toxoid (TT), and purified protein derivate of mycobacterium tuberculosis (PPD). These findings indicate a decreased total gp120 content in serum, permitting better T-cell activation.

Adult↗

Human immunodeficiency virus type 1 and cytomegalovirus in saliva.

The aim of this study was to evaluate whether HIV-1 or cytomegalovirus (CMV) may contribute to oral lesions frequently found in patients with the acquired immunodeficiency syndrome (AIDS). Saliva samples from 63 HIV-1 positive patients and 21 healthy controls were tested for the presence of HIV-1 and CMV using the polymerase chain reaction (PCR) and virus isolation. CMV IgG titres in serum were also compared in the different groups. HIV-1 RNA, but not DNA, was detected in saliva from 15% (9 out of 59) of the HIV-infected patients. There was no correlation between the presence of HIV-1 RNA and oral symptoms in the patients. CMV DNA was detected significantly more frequently in samples from HIV-1 seropositive than from seronegative patients. CMV was detected in saliva from AIDS patients more often than in saliva from patients with mild or no symptoms. CMV IgG titres were also significantly higher in symptomatic than in asymptomatic patients. There was a significant correlation between the presence of CMV DNA and necrotizing gingivitis, and oral Kaposi's sarcoma in the patients, and also between these lesions and the stage of disease. This does not prove that CMV causes these oral lesions, but a direct or indirect role for CMV cannot be excluded.

Acquired Immunodeficiency Syndrome↗

Antiviral therapy in human immunodeficiency virus infections. Current status (Part I).

Antiviral therapy has in the past met with limited success and only a few antiviral drugs have been available. The human immunodeficiency virus (HIV) epidemic has created an urgent need for the development of antiviral therapy against this infection. HIV replication offers several targets for inhibitory compounds, the foremost presently being the HIV reverse transcriptase and protease enzymes. Despite the short time since the beginning of the epidemic, 3 nucleoside analogue drugs (zidovudine, didanosine and zalcitabine) which act at the reverse transcriptase site are already licensed for use against HIV, and others (stavudine, alovudine and 3-TC) are still under clinical evaluation. Part II of this article discusses non-nucleoside reverse transcriptase inhibitors undergoing investigation, protease inhibitors, and compounds active against various other targets in HIV. Treatment guidelines are also provided in Part II.

Animals↗

Antiviral therapy in human immunodeficiency virus infections. Current status (Part II).

Part I of this article reviewed the targets against which anti-HIV drugs can be directed, problems in assessing active compounds (e.g. resistance development and use of surrogate end-points). and nucleoside analogues effective against HIV reverse transcriptase. Intensive research is currently being undertaken in laboratories and hospitals to design and evaluate new inhibitors of HIV. In this work, combining different drugs is one important approach, both to decrease toxicity and to offset the rate of resistance development, which seems to be a major problem associated with therapy directed against the ever-changing HIV. Therapeutic vaccines and immunomodulators are other modalities being actively evaluated against HIV and AIDS, although this effort has not yet yielded any licensed treatment. It appears likely that new antiviral drugs and immunotherapies will be forthcoming during the next 5 years, that they will be used in a variety of combinations, and that the treatment options available for opportunistic infections will increase. These developments should improve the survival and the quality of life of patients with HIV infection.

Antiviral Agents↗

Effects of adjuvants and multiple antigen peptides on humoral and cellular immune responses to gp160 of HIV-1.

The capacity of five different adjuvants, AlPO4, a muramyldipeptide formulation (MDP.TSL), Freund's adjuvant, immunostimulating complex and its matrix components to elicit humoral and cellular responses in rabbits immunized with the human immunodeficiency virus type 1 (HIV-1) envelope protein rgp160IIIB was compared. The highest antibody titers against gp160 and gp41/gp120 epitopes were seen with rgp160 in MDP.TSL or Freund's adjuvant, whereas the broadest responses were seen in rabbits immunized with rgp160 in matrix or MDP.TSL. The broadest spectrum of high-avidity antibodies was also induced by rgp160 in MDP.TSL. Neutralizing titers against HIV-1IIIB, low titers to HIV-1MN, and the most efficient inhibition of viral cell-to-cell spread was seen with rgp160 in MDP.TSL. The strongest and most persisting cellular responses were induced by rgp160 in AlPO4 or MDP.TSL. Using MDP.TSL as the adjuvant, we also improved the immune response against gp120 epitopes by boosting rgp160-primed rabbits with rgp160, multiple antigenic peptides (MAPs), or unconjugated peptides. The MAPs induced high neutralizing titers and were superior to rgp160 alone in inducing both humoral and cellular reactivity. MAPs are therefore strong candidates for inclusion into future HIV-1 vaccines.

Acetylmuramyl-Alanyl-Isoglutamine↗