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Biomedical subjects

Eric Sandström

Publications and source records attributed to Eric Sandström.

17 recordsLinked to original sources
PubMed2007

The epidemiology of gonorrhea among men who have sex with men in Stockholm, Sweden, 1990-2004.

OBJECTIVES: The objectives of this study were to analyze the spread of gonorrhea in men who have sex with men (MSM) in Stockholm regarding serovars, HIV status, and site of infection and to compare the distribution of serovars among HIV-positive and HIV-negative MSM. STUDY DESIGN: Clinical and epidemiologic data were collected for all MSM diagnosed with gonorrhea in 1990 to 2004 at a clinic primarily serving MSM. Neisseria gonorrhoeae strains were serotyped. RESULTS: A total of 1,039 isolates from 840 gonorrhea episodes in 721 patients were included. A sharp increase was seen during the 2000s. Ten percent of the cases were HIV-positive. The proportion of pharyngeal infections increased significantly (P <0.001) from 15% to 38% during the last 7 years. A great variation of serovars (n = 66) was observed, but only 5 were present >10 years. There was a significant difference (P = 0.001) in distribution of serovars correlated to HIV status. CONCLUSION: Gonorrhea is a marker for HIV infection in MSM, but the increase in gonorrhea may be associated with genital-oral sexual practice rather than with high-risk sexual practice.

Gonorrhea↗
PubMed2006

Antiretroviral treatment of HIV infection: Swedish recommendations 2005.

On 2 earlier occasions, in 2002 and 2003, the Swedish Medical Products Agency (MPA) and the Swedish Reference Group for Antiviral Therapy (RAV) have jointly publicized recommendations for the treatment of HIV infection. A working group from the same expert team that produced the 2002 report has now revised the text again. Since the publication of the last treatment recommendations, 4 new medicines have become available: emtricitabine, atazanavir, fosamprenavir, and enfuvirtid. The last-mentioned belongs to a new class of HIV medications called fusion inhibitors (Box 1). It is likely that tipranavir will also be on the market soon. Simultaneously, the drug zalcitabin has been deregistered. The following updated recommendations parallel the earlier ones, but increased knowledge allows us to be more specific in our recommendations. Thus, it is now suggested that the initial treatment for HIV infection consist of 2 nucleoside reverse transcriptase inhibitors (NRTIs) and 1 non-nucleoside reverse transcriptase inhibitor (NNRTI); or 2 NRTIs and 1 protease inhibitor (PI). In the group of the NRTIs, stavudine is no longer recommended for this purpose. In the NNRTI group, efavirenz should be preferred to nevirapine, except under special circumstances. Finally, PIs ought to be boosted with ritonavir (PI/r). Also new are recommendations regarding treatment choices for patients co-infected with hepatitis B virus (HBV) or tuberculosis (TB). As in the case of the previous publication, recommendations are evidence-graded in accordance with the Oxford Centre for Evidence Based Medicine, 2001 (see http://www.cebm.net/levels_of_evidence.asp#levels), and have been supplemented with references to newly-added sections and data not referred to in earlier background documentation.

Anti-Retroviral Agents↗
PubMed2006

Human immunodeficiency virus-type 1 specific cellular immunity in chronic infected patients on prolonged highly active antiretroviral treatment and on structured treatment interruption.

We have followed 15 HIV-1 chronically infected patients during prolonged highly active antiretroviral treatment (HAART) and subsequent long term structured treatment interruption (STI). We analyzed Nef, Tat, and p24 specific cellular immunity using IFN-gamma enzyme-linked immunospot assays and T cell proliferation assays. Eight HAART patients showed IFN-gamma responses to at least one antigen, but no positive responses were seen during STI. We observed retained or increased p24 specific IFN-gamma responses in most patients during HAART with viral suppression. These results showed persisting HIV-1 specific cellular immunity during HAART; however, in prolonged STI with viral rebound this immunity declined.

Anti-HIV Agents↗
PubMed2005

The two-year impact of first generation protease inhibitor based antiretroviral therapy (PI-ART) on health-related quality of life.

BACKGROUND: Protease inhibitor based antiretroviral therapy (PI-ART) was introduced in 1996 and has greatly reduced the incidence of HIV-related morbidity and mortality in the industrialised world. PI-ART would thus be expected to have a positive effect on health-related quality of life (HRQL). On the other hand, HRQL might be negatively affected by strict adherence requirements as well as by short and long-term adverse effects. The aim of this study was to assess the influence of two years of first generation PI-ART on HRQL in patients with a relatively advanced state of HIV-infection. Furthermore, we wanted to investigate the relation between developments in HRQL and viral response, self-reported adherence and subjective experience of adverse effects in patients with PI-ART. METHODS: HRQL was measured by the Swedish Health-Related Quality of Life Questionnaire (SWED-QUAL). Sixty-three items from the SWED-QUAL forms two single-item and 11 multi-item dimension scales. For this study, two summary SWED-QUAL scores (physical HRQL composite score and emotional HRQL composite score) were created through a data reduction procedure. At the 2-year follow-up measurement (see below), items were added to measure adherence and subjective experience of adverse effects. Demographic and medical data were obtained from specific items in the questionnaires and from the medical files. Seventy-two patients who were among the first to receive PI-ART (indinavir or ritonavir based) responded to the questionnaire before the start of PI-ART. Of these, 54 responded to the same instrument after two years of treatment (13 had died, four had changed clinic and one did not receive the questionnaire). RESULTS: The main findings were that the emotional HRQL deteriorated during two years of PI-ART, while the physical HRQL remained stable. Multiple linear regression analyses showed that experience of adverse effects contributed most to the deterioration of emotional HRQL. CONCLUSION: In this sample of patients with relatively advanced state of HIV-infection, our data suggested that a negative development of physical HRQL had been interrupted by the treatment and that the emotional dimension of HRQL deteriorated during two years after start of PI-ART. Subjective experience of adverse effects made a major contribution to the decrease in emotional HRQL. The results underline the importance of including HRQL measures in the evaluation of new life prolonging therapies.

Adult↗
PubMed2005

A novel assay for assessment of HIV-specific cytotoxicity by multiparameter flow cytometry.

BACKGROUND: Assessment of CD8(+) T-cell activity is of significant importance for the evaluation of cellular immune responses to viral infections, especially in HIV. We present a new assay for the assessment of HIV-specific cytotoxicity by multiparameter flow cytometry. METHODS: Target cells, pulsed with peptide pools (Gag or Nef), were stained with 5- (and -6)-carboxyfluorescein diacetate succinimidyl ester (CFSE), cultured with specific or nonspecific effector cells, and finally stained with propidium iodide (PI). Determination of cytolysis is based on the enumeration of viable target cells (CFSE(hi)PI(-)) in the test sample (target and specific effector cells) as compared with that of the viable target cells in the control sample (target and nonspecific effector cells). The (51)Cr-release assay and IFN-gamma ELISpot were performed by standard procedures. RESULTS: A comparison with the Cr-release showed that the two assays were strongly correlated (r = 0.67; P < 0.001) but the sensitivity of the flow cytometric assay was significantly higher (P < 0.05), and the reproducibility good (CV, 7.7%). Good correlation was also found with the ELISpot assay (r = 0.66; P < 0.01). CONCLUSION: This new assay provides both specific and sensitive results when employed for the detection of HIV-specific CTL and can be a valuable tool for the evaluation of cytolytic activity in vaccine trials or in HIV-infected subjects, especially if such responses are present at low levels.

Cells, Cultured↗
PubMed2005

Improved HIV-1 viral load determination based on reverse transcriptase activity recovered from human plasma.

A more sensitive version of ExaVir Load, a test that utilizes reverse transcriptase (RT) activity from virions in plasma to determine HIV-1 viral load, is described. The virions were immobilized on a gel that was washed, followed by lysis of the virions, elution of purified RT, and finally RT activity determination. The changes made to the original test were: (1) improved washing of the immobilized virions by addition of a non-lytic detergent to the wash buffer, (2) improved virion lysis procedure, including changes in salt, detergent and pH, (3) the use of larger sample volumes in the RT assay, and (4) prolonged RT reaction time. The alterations gave a tenfold increased sensitivity compared to the original version. The correlation between RT load by the current test and RNA PCR was the same as previously (r=0.90). Using colorimetric product detection, the average detection limit in a panel of 262 patient plasma from Stockholm was 0.5 fg RT/ml, corresponding to approximately 170 RNA copies/ml. None of 54 HIV-1 RNA negative samples exhibited RT. The amount of RT load positive samples were 19% for samples containing 50-400 RNA, 71% for samples with 400-1,500, and 100% among samples with >8,000 copies/ml (according to Roche Amplicor). The sensitivity could be increased further using fluorimetric detection. In conclusion, the modifications of the test described result in an important increase in sensitivity. It can now be regarded as a competitive alternative method for HIV viral load determinations.

Fluorometry↗
PubMed2004

[Increasing incidence of ciprofloxacin resistant gonorrhea in Sweden. Choose a correct antibiotic and follow up the treatment!].

The incidence of gonorrhoea has increased in Sweden and is now three times higher than in the middle of the 1990's. A remarkable increase of ciprofloxacin resistant gonorrhoea has been reported in Stockholm and other parts of Sweden during 2003. Among men attending a clinic for homosexual men in Stockholm the ciprofloxacin resistant cases have increased from a low level to over 50% during the last year. Most of the homosexual men are exposed in Stockholm and one serotype is dominant. Also in the county of Gävleborg there has been an outbreak of ciprofloxacin resistant gonorrhoea among young heterosexual men and women. No resistance to cefixime, ceftriaxone and spectinomycin has been noted and these antibiotics are then a better first choice of treatment in a Swedish context.

Anti-Infective Agents↗
PubMed2004

Long-term persistence of vaccination and HAART to human immunodeficiency virus (HIV).

The aim of this study was to monitor the immune responses in HIV-infected patients previously immunized with gp160 or DNA vaccines to analyze whether the introduction of highly active antiretroviral treatment (HAART) would affect the persistence of immunity. The immune responses were evaluated in patients who had participated in randomized trials of therapeutic vaccination. Immunization in conjunction with antiretroviral therapy was effective in inducing HIV-specific T-cell responses. Therapeutic immunizations with recombinant gp160 had a modest effect on CD4-cell counts, the treatment alone lead to a transient clinical benefit in the form of an improved survival after two years of immunization. Immunizations with HIV DNA during HAART treatment permitted persistence or development of innate (NK), CD4+ and/or CD8+ immune responses. HIV specific T-helper cell responses induced by immunization with gp160 were maintained at high levels up to 7 years after the last injection. Cells with HIV-specific interferon-gamma (IFN-gamma) production were retained or increased in long-term HAART treated patients. The impact of a single structured therapy interruption (STI) was analyzed in a small group of patients showing no obvious increase or decrease in the HIV-specific immune response during or after STI. The possibility to induce very long-term strong and persistent immune responses in HIV-infected individuals raises hopes that vaccination preceding therapy interruption might prolong the symptom-free period without HAART.

AIDS Vaccines↗
PubMed2004

Topical delivery of imiquimod to a mouse model as a novel adjuvant for human immunodeficiency virus (HIV) DNA.

We evaluated the compound imiquimod as a possible adjuvant for DNA immunization against human immunodeficiency virus (HIV). We found that gene-gun epidermal delivery of the DNA in combination with imiquimod resulted in the strongest HIV specific immune responses. The effect of imiquimod was further compared to that of recombinant granulocyte macrophage-colony stimulating factor (GM-CSF), a known DNA vaccine adjuvant. Both adjuvants were able to enhance the immune responses induced by the HIV-1 genes alone. The delivery of an adjuvant as a topical cream rather than through injections has a clear clinical benefit. We show for the first time that imiquimod can act as an adjuvant for DNA vaccination.

AIDS Vaccines↗
PubMed2004

Rate of decline of absolute number and percentage of CD4 T lymphocytes among HIV-1-infected adults in Dar es Salaam, Tanzania.

OBJECTIVE: To determine the rate of decline of CD4 T lymphocytes among HIV-1-infected individuals. DESIGN AND SETTING: A prospective open cohort study of workers in three hotels in Dar es Salaam. METHODS: The workers were seen yearly during the study. CD4 T lymphocyte counts were determined using flow cytometry. The CD4 T-lymphocyte slopes were determined using a linear regression model. RESULTS: During the 9-year study period 682 subjects were selected for lymphocyte subset determinations. Of these, 94 HIV-1-seroprevalent (72%), 77 HIV-1-seroincident (67%) and 325 seronegative (75%) individuals had three or more CD4 T-cell determinations, and were used for calculations of CD4 cell slopes with a mean follow-up period of 71.4, 52.9 and 86.0 months, respectively. The median yearly decline of the CD4 T-lymphocyte counts and percentages among seroprevalent individuals was -21.5 cells/microl and -1.3%; among the seroincident individuals the median decline was -22.0 cells/microl and -1.5%. In seroincident individuals the mean duration to a CD4 T-lymphocyte level corresponding to a definition of AIDS was 13.3 years or 11.8 years for CD4 cell counts or percentages, respectively. HIV-1-seropositive subjects who died had significantly steeper CD4 cell slopes than those who survived. CONCLUSION: The rates of CD4 T-lymphocyte decline in HIV-1-infected individuals in our population are similar to those reported in Europe and north America.

Adult↗
PubMed2004

The reverse transcriptase (RT) mutation V118I is associated with virologic failure on abacavir-based antiretroviral treatment (ART) in HIV-1 infection.

Antiviral efficacy and serum lipids were investigated following a switch from long-term successful protease inhibitor based antiretroviral treatment (PI-ART) to abacavir-based ART in 29 patients who have been followed for 28 months thereafter. Virologic failure occurred within 3 months in 21% (6/29) of the patients, and abacavir hypersensitivity in 1 individual. The remaining 22 patients continue to have HIV RNA < 50 copies/ml after 28 months with a CD4 increase from 605 +/- 265 x 10(6)/l to 798 +/- 366 x 10(6)/l (p < 0.001). All virologic failing patients had been on long-term unsuccessful nucleoside reverse transcriptase inhibitor (NRTI) therapy before PI-ART as compared to 32% (7/22) of the virologic non-failing patients (p < 0.01). The viral strains from the virologic failing patients harboured 3-6 reverse transcriptase (RT) mutations, including the V118I mutation in 5/6 cases prior to PI-ART or at viral rebound. Only the V118I RT mutation was statistically more common among virologic failing than non-failing NRTI pretreated patients (p < 0.05). Stepwise multiple regression analysis for viral failure resulted in a model with only the V118I RT mutation entering the model (p < 0.01). The LDL cholesterol and triglyceride values decreased and the HDL cholesterol increased after the switch to abacavir-based ART (p < 0.01, p < 0.05, p < 0.05, respectively). In conclusion, viral failure was associated with prior mono- or dual-NRTI treatment and the occurrence of the V1181 RT mutation, persisting despite long term viral control. The selection process for patients suitable for treatment simplification to abacavir-based ART should contain a detailed antiretroviral treatment history.

Adult↗
PubMed2004

The natural course of disease following HIV-1 infection in dar es salaam, Tanzania: a study among hotel workers relating clinical events to CD4 T-lymphocyte counts.

Current HIV management guidelines are based on natural history studies from the developed world. Data on the similarity of the natural course of HIV-1 infection conflict with studies in the developing world. A cohort of 1887 hotel workers with no access to antiretroviral therapy was followed between 1990 and 1998 in Dar es Salaam through annual clinical evaluations and CD4+ T-lymphocyte (CD4 cell) count determinations. 196 (10.4%) were HIV-1 sero-prevalents; 133 (7.9%) were HIV-1 sero-incidents; and 1558 (82.6%) remained HIV seronegative. Follow-up duration was 13,719 and 82,742 months for HIV-1 seropositives and HIV seronegatives respectively. Clinical events occurred at median CD4 cell counts similar to those previously reported from the developed world, but death occurred at higher counts. Off-duty last 6 months, chronic diarrhoea and a faster CD4 cell count decline were associated with faster disease progression and death. In Tanzania HIV natural history is similar to that from the developed world and similar management guidelines could be employed.

Adult↗
PubMed2003

HIV-1 viral load determination based on reverse transcriptase activity recovered from human plasma.

We describe a procedure (ExaVir Load) to carry out human immunodeficiency virus-1 (HIV-1) viral load testing using reverse transcriptase (RT) recovered from HIV-1 virions in plasma. Samples from individuals infected with HIV-1 were treated with a sulphydryl-reactive agent to inactivate endogenous polymerases. Virions were then immobilised on a gel and washed in individual mini columns to remove RT-inhibiting antibodies, antiviral drugs, and other RT inhibitors. Immobilised virions were lysed finally, and the viral RT eluted. The amount of RT recovered was quantified by a sensitive RT activity assay using either colorimetry or fluorimetry to detect DNA produced by RT. The "RT load" values of 390 samples from 302 HIV-1 patients living in Sweden were compared to results obtained with an HIV-1 RNA viral load assay. The correlation between the two tests was r = 0.90, P < 0.0001. Four of 202 samples from healthy blood donors gave low positive values in the RT test. All samples in a panel with 10 HIV-1 subtypes were positive by the RT load. The RT load test provides a technically less demanding and cost-effective alternative to methods based on nucleic acid amplification. Being insensitive to genetic drift occurring in HIV, the assay should be of particular use in resource-limited settings, where different subtypes and recombinant HIV strains occur.

Animals↗
PubMed2003

Antiretroviral treatment of human immunodeficiency virus infection: Swedish recommendations.

The Swedish guidelines (SwG) for treatment of human immunodeficiency virus (HIV) infection have several important roles. A major task involves the promotion of a uniformly high standard of care in all HIV treatment clinics in Sweden and the identification of strengths, weaknesses and relevance of recent research findings. CD4+ T-cell counts < 200 cells/microl are clear indications for the initiation of treatment, whereas high viral loads serve as an indication for increased vigilance rather than a criterion for therapy. It is recommended that the first regimen consists of 2 nucleoside reverse transcriptase inhibitors in combination with 1 protease inhibitor or 1 non-nucleoside reverse transcriptase inhibitor. The definition of treatment failure is rigorous. Treatment change should be considered if the viral load has not fallen by at least 1.5 log in 4 weeks or is undetectable within 3-4 months. Resistance testing is endorsed at primary infection, in the event of treatment failure and in pregnant women. Interaction with experts in HIV resistance testing is emphasized. Therapeutic drug monitoring is advocated. Patients with treatment failure should be handled individually and the decision on therapeutic strategy should be based on treatment history, resistance testing and other clinical facts. The SwG do not give recommendations for some important issues such as prolonged drug holidays and preferences in initial treatment regimens. More scientific data are likely to be available soon and the SwG will be refined accordingly. The present guidelines are translated from Swedish; they are published on the Medical Products Agency (MPA) and Swedish Reference Group for Antiviral Therapy (RAV) websites (www.mpa.se and www.rav.nu.se), including 7 separate papers based on a thorough literature search. A complete reference list is available on request from the MPA.

Anti-HIV Agents↗
PubMed2002

Hypofibrinolytic state in HIV-1-infected patients treated with protease inhibitor-containing highly active antiretroviral therapy.

Decreased insulin sensitivity, hyperlipidemia, and body fat changes are considered as risk factors for coronary heart disease (CHD). A clustering of such factors (metabolic syndrome [MSDR]) exponentially increases the risk. Impaired fibrinolysis and increased coagulation are additional independent risk factors for CHD. We studied the effects of protease inhibitor (PI)-containing highly active antiretroviral therapy (HAART) on metabolic and hemostatic parameters in 363 HIV-infected individuals, of whom 266 were receiving PI-containing HAART and 97 were treatment naive. The fasting plasma levels of insulin, glucose, triglycerides, cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, plasminogen activator inhibitor type 1 (PAI-1), and fibrinogen were evaluated together with the areas of visceral adipose tissue and the visceral adipose tissue/subcutaneous adipose tissue area ratio. The levels of insulin, triglycerides, cholesterol, and low-density lipoprotein cholesterol; visceral adipose tissue area; low-density lipoprotein/high-density lipoprotein ratio; and visceral adipose tissue/subcutaneous adipose tissue area ratio were significantly increased in patients receiving PI-containing HAART compared with treatment-naive patients. The levels of PAI-1 and fibrinogen were significantly higher in patients receiving PI-containing HAART. PAI-1 levels were higher in individuals with MSDR but also in patients without MSDR who were receiving PI-containing HAART. PAI-1 was independently correlated to use of PI-containing HAART, triglyceride level, insulin level, and body mass index (p <.001). These findings suggest that patients receiving PI-containing HAART have decreased fibrinolysis and increased coagulability, which may thus represent additional risk factors for cardiovascular disease in this patient group.

Adipose Tissue↗
PubMed2002

DNA mucosal HIV vaccine in humans.

This is a demonstration of immune activation by delivery of genetic vaccines in human mucosa. We analyzed the local and systemic responses in HIV-1 infected individuals following intraoral jet-injections of HIV-1 DNA constructs encoding the nef, rev, and tat regulatory genes. The immunological responses of the oral mucosa may be representative of other mucosal sites and was therefore selected for induction of mucosal reactivity by DNA immunization. The oral and intramuscular routes induced specific systemic T cell proliferative responses. Immunohistochemical analysis of oral biopsies 2 days after immunization revealed increased levels of granulocytes and T cells as well as expression of HLA-DR. T cell markers for CD3 +, CD4 + and CD8 + were significantly increased in the vaccinated mucosa. Vaccine-specific local and systemic antibodies were present during the immunization. However, increases were neither seen in the local or systemic titer nor in the B-cell accumulation in response to the immunizations. The presence of HIV-1 plasmid DNA was observed in mucosal biopsies as well as local proinflammatory T lymphocyte immune responses with predominantly IL-2 expression in the oral mucosal transudate.

AIDS Vaccines↗