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Biomedical subjects

L Perrin

Publications and source records attributed to L Perrin.

At least 55 records · Page 3Linked to original sources
PubMed2000

Prevalence and characteristics of multinucleoside-resistant human immunodeficiency virus type 1 among European patients receiving combinations of nucleoside analogues.

The prevalence and the genotypic and phenotypic characteristics of multinucleoside-resistant (MNR) human immunodeficiency virus type 1 (HIV-1) variants in Europe were investigated in a multicenter study that involved centers in nine European countries. Study samples (n = 363) collected between 1991 and 1997 from patients exposed to two or more nucleoside analogue reverse transcriptase inhibitors (NRTIs) and 274 control samples from patients exposed to no or one NRTI were screened for two marker mutations of multinucleoside resistance (the Q151M mutation and a mutation with a 2-amino-acid insertion at codon 69, T69S-XX). Q151M was identified in six of the study samples (1. 6%), and T69S-XX was identified in two of the study samples (0.5%; both of them T69S-SS), but both patterns were absent among control samples. Non-NRTI (NNRTI)-related changes were observed in viral strains from two patients, which displayed the Q151M resistance pattern, although the patients were NNRTI naive. The patients whose isolates displayed multinucleoside resistance had received treatment with zidovudine and either didanosine, zalcitabine, or stavudine. Both resistance patterns conferred broad cross-resistance to NRTIs in vitro and a poor response to treatment in vivo. MNR HIV-1 is found only among multinucleoside-experienced patients. Its prevalence is low in Europe, but it should be closely monitored since it seriously limits treatment options.

Amino Acid Substitution↗
PubMed2000

Predicting the duration of antiviral treatment needed to suppress plasma HIV-1 RNA.

Effective therapeutic interventions and clinical care of adults infected with HIV-1 require an understanding of factors that influence time of response to antiretroviral therapy. We have studied a cohort of 118 HIV-1-infected subjects naive to antiretroviral therapy and have correlated the time of response to treatment with a series of virological and immunological measures, including levels of viral load in blood and lymph node, percent of CD4 T cells in lymph nodes, and CD4 T-cell count in blood at study entry. Suppression of viremia below the limit of detection, 50 HIV-1 RNA copies/mL of plasma, served as a benchmark for a successful virological response. We employed these correlations to predict the length of treatment required to attain a virological response in each patient. Baseline plasma viremia emerged as the factor most tightly correlated with the duration of treatment required, allowing us to estimate the required time as a function of this one measure.

Adult↗
PubMed1999

High frequency of non-B subtypes in newly diagnosed HIV-1 infections in Switzerland.

HIV-1 subtypes were determined in newly diagnosed residents of Switzerland. Blood was anonymously collected from patients with a first confirmed positive HIV-1 test result. Viral DNA from the env V3-V5 region was amplified by nested polymerase chain reaction (PCR) and screened for subtype B by heteroduplex mobility assay. All amplicons not identified as B were sequenced. From November 1996 to February 1998, 206 samples were analyzed. Main transmission risks were unprotected heterosexual (55.7%) or homosexual (27.1%) sexual contact or intravenous drug use (12.9%). Subtype B dominated in patients of Swiss, other European, American, or Asian citizenship; particularly high frequencies were found in homosexuals (97%) and drug users (94%). Non-B subtypes including A, C, D, E, F, G, H, a possible B/F recombinant, and a sequence related to J were present in 28.2% (95% confidence interval [CI], 22.9%-35.0%). Non-B were frequent in African citizens (95%), heterosexually infected individuals (44%), and women (43%). Heterosexually infected Swiss males harbored non-B strains in 18% and females in 33%. The results document a change in the epidemiology of newly diagnosed HIV-1 infections in Switzerland: predominance of heterosexual transmission and a high frequency of non-B subtypes.

Adult↗
PubMed1999

Transmission of antiretroviral-drug-resistant HIV-1 variants.

BACKGROUND: Resistance of HIV-1 to antiretroviral drugs is the main cause of antiretroviral-treatment failure. We assessed the transmission of drug-resistant variants among individuals with primary HIV-1 infection. METHODS: Population-based sequencing of the viral reverse-transcriptase and protease genes derived from plasma viral RNA was done in 82 consecutive individuals with documented primary HIV-1 infection from January, 1996, to July, 1998. Phenotypic resistance to protease inhibitors was assessed by recombinant virus assay in individuals with two or more mutations associated with resistance to protease inhibitors. FINDINGS: Zidovudine-resistance mutations were detected in seven (9%) of 82 individuals. Mutations associated with resistance to other reverse-transcriptase inhibitors (RTIs) were detected in two individuals. Primary-resistance mutations associated with protease inhibitors (V82A, L90M) were detected in three (4%) of 70 individuals; two of these had also RTI-resistance mutations. Decreased sensitivity to three or four protease inhibitors was seen in three individuals, one of whom was infected with HIV-1 variants that harboured 12 mutations associated with resistance to multiple RTI and protease inhibitors. INTERPRETATION: To introduce the best antiretroviral treatment, resistance testing should be done in recently HIV-1-infected individuals.

Adolescent↗
PubMed1999

Comprehensive classification of symptoms and signs reported among 218 patients with acute HIV-1 infection.

Acute HIV-1 illness presents a wide range of clinical manifestations. We assessed a classification and data reduction of clinical features among 218 patients with acute HIV-1 infection enrolled in four prospective seroincidence studies. Factor analysis allows the definition of eight factors based on groups of symptoms and signs: gastrointestinal transit disturbances, weight loss/abdominal pain, lymphadenopathy, myalgia/arthralgia, neurologic features, constitutional and mucocutaneous features, oral candidiasis, and anorexia/pharyngitis. These groups reflected the main target systems involved at the time of acute HIV-1 disease. Grouping of symptoms and signs based on groups of patients is potentially more informative than observations made on individual patients. It might facilitate diagnosis, suggest pathogenic mechanisms and reduce the number of variables for characterizing acute HIV-1 illness.

Acute Disease↗
PubMed1999

The Drosophila modifier of variegation modulo gene product binds specific RNA sequences at the nucleolus and interacts with DNA and chromatin in a phosphorylation-dependent manner.

modulo belongs to the modifier of Position Effect Variegation class of Drosophila genes, suggesting a role for its product in regulating chromatin structure. Genetics assigned a second function to the gene, in protein synthesis capacity. Bifunctionality is consistent with protein localization in two distinct subnuclear compartments, chromatin and nucleolus, and with its organization in modules potentially involved in DNA and RNA binding. In this study, we examine nucleic acid interactions established by Modulo at nucleolus and chromatin and the mechanism that controls the distribution and balances the function of the protein in the two compartments. Structure/function analysis and oligomer selection/amplification experiments indicate that, in vitro, two basic terminal domains independently contact DNA without sequence specificity, whereas a central RNA Recognition Motif (RRM)-containing domain allows recognition of a novel sequence-/motif-specific RNA class. Phosphorylation moreover is shown to down-regulate DNA binding. Evidence is provided that in vivo nucleolar Modulo is highly phosphorylated and belongs to a ribonucleoprotein particle, whereas chromatin-associated protein is not modified. A functional scheme is finally proposed in which modification by phosphorylation modulates Mod subnuclear distribution and balances its function at the nucleolus and chromatin.

Animals↗
PubMed1999

[Post-exposure HIV prevention: eligibility of patients recently infected by sexual exposure].

QUESTION: Post-exposure prophylaxis (PEP) is effective in preventing HIV infection after professional exposure. PEP is also recommended after inadvertent sexual exposure if two conditions are met: the source person is known to be HIV infected, and exposure to this person occurred only once or is accidental. The objective of this study is to describe the circumstances of sexual exposure and determine how frequently these conditions were present among patients diagnosed during primary HIV infection. METHODS: Physicians of 35 patients diagnosed with primary HIV infection provided detailed information on the circumstances of infection as well as on the patients and source persons. RESULTS: Most patients were homosexual (71%), and 91% were male. Only one patient (3%) had a single exposure with a known HIV-infected person and was therefore eligible for PEP. Eight patients (23%) who did not know the HIV status of their partner would have been eligible considering single exposure as a sufficient criterion for PEP. Oro-genital contact appears to account for transmission in four instances. Eleven persons (31%) were infected after sexual contact with their stable partner, of whom 7 did not known his/her HIV status. Twelve patients (34%) were infected after multiple unprotected sexual contact with unknown partners. CONCLUSION: The direct impact of PEP in terms of HIV infections prevented is likely to be small. PEP will not make up for the failure of other prevention methods. It may, however, contribute to the disclosure and the discussion of risk situations and help physicians provide individual counselling taking into account the precise context of risk behavior.

Adult↗
PubMed1999

[Early diagnosis of primary HIV infections: using a combined screening test (p24 antigen and anti-HIV antibodies)].

Laboratory diagnosis of HIV infection is based on the detection of HIV antibodies. There is a delay between infection and seroconversion (i.e. the appearance of specific HIV antibodies) corresponding to a window period which may last several weeks. Reduction of the length of the window period might be achieved by using p24 antigen and/or viral nucleic acid detection assays. We have evaluated a new screening assay (VIDAS HIV DUO) designed for the concurrent detection of HIV antibodies and p24 antigen, using sequential samples of 34 HIV-1 seroconverting patients and 236 HIV-positive samples confirmed by Western blot. Results were compared with those obtained with two third-generation anti-HIV antibody screening assays. The 236 confirmed HIV-positive samples including 3 HIV-1 subtype O and 2 HIV-2 samples were found to be positive by the 3 assays. All 128 sequential samples from 34 seroconverting patients were found to be positive using the DUO assay, including 20/20 pre-seroconversion samples (p24 antigen-positive and anti-HIV negative). The new screening assay was positive before a third-generation anti-HIV screening assay gave positive results in 14/34 patients (41%). Using the DUO assay, the mean reduction of the window period was 4 days.

AIDS Serodiagnosis↗
PubMed1999

Impact of drug resistance mutations on virologic response to salvage therapy. Swiss HIV Cohort Study.

OBJECTIVE: To assess the prognostic significance of drug-associated mutations in the protease and reverse transcriptase (RT) genes on virological response to salvage therapy. PATIENTS: All patients from four centres of the Swiss HIV Cohort Study who were switched, between February and October 1997, to nelfinavir plus other antiretroviral drugs following failure of highly active antiretroviral therapy (HIV-1 RNA >1000 copies/ml after > 3 months). METHODS: Direct sequencing of RT and protease genes derived from plasma RNA was performed in 62 patients before salvage therapy. Baseline predictors (drug-resistance mutations, drug exposure, clinical and biological parameters) of virological response after 4-12 weeks of therapy were assessed by linear regression analyses. RESULTS: Patients had been treated with RT inhibitors and protease inhibitors for a median duration of 35.6 and 12.2 months, respectively. Baseline median CD4 cell count was 113 x 10(6)/l and HIV-1 RNA 5.16 log10 copies/ml. The median decrease of HIV-1 RNA was 0.38 log10; 32% of the patients showed > 1 log10 decrease. At baseline, 90% of the patients had RT inhibitor-resistance mutations with a median number per patient of four (range, 0-7). Primary and secondary protease inhibitor-resistance mutations were detected in 69% and 89% of the patients, respectively. The median number of total protease inhibitor-resistance mutations per patient was four (range, 0-9). In univariate analysis, virological response to salvage therapy was associated with number of RT inhibitors, primary and secondary protease inhibitor-resistance mutations, history of protease inhibitor use (duration and number), but not with clinical stage, HIV-1 RNA level or CD4 cell count. After adjustment for all variables, the number of RT inhibitor plus protease inhibitor-resistance mutations was the only independent predictor. CONCLUSIONS: In patients with advanced HIV infection, the virological response to salvage therapy containing nelfinavir is best predicted by the number of baseline RT inhibitor plus protease inhibitor-resistance mutations.

Anti-HIV Agents↗
PubMed1999

Codon 215 mutations in human immunodeficiency virus-infected pregnant women. Swiss Collaborative 'HIV and Pregnancy' Study.

In 1994, the Pediatric AIDS Clinical Trials Group (PACTG) Protocol 076 demonstrated a two-thirds reduction of perinatal human immunodeficiency virus (HIV) type 1 transmission with zidovudine chemoprophylaxis. However, zidovudine alone does not fully suppress HIV replication, and chemoprophylaxis with zidovudine alone might select for zidovudine-resistant viral variants, decreasing the efficacy of zidovudine prophylaxis and affecting future responses to combined antiretroviral regimens. Sixty-two HIV-infected pregnant women consecutively enrolled in the ongoing Swiss HIV and Pregnancy Study were prospectively evaluated for the presence or development of zidovudine resistance by analysis of codon 215 of the reverse transcriptase gene. Six women (9.6%) harbored a codon T215Y/F mutation, which is associated with high-level resistance to zidovudine. Postnatal evaluation was completed in all children of mothers harboring the mutation. None was HIV-infected. The observed prevalence of codon 215 mutations of 9.6% raises important concerns regarding the future use of the PACTG 076 regimen.

Amino Acid Substitution↗
PubMed1999

Cell-associated HIV-1 RNA in blood as indicator of virus load in lymph nodes. The Swiss HIV Cohort Study.

We have developed sensitive assays for viremia and cell-associated human immunodeficiency virus type 1 (HIV-1) RNA and DNA to assess the predictive value of virological parameters determined in blood for virus load in lymph nodes (LNs). Eighteen patients were included; 13 received stavudine/didanosine/hydroxyurea and 5 stavudine/didanosine, and all had viremia <500 copies/mL for >3 months. At the time of LN biopsy (median, 10 months), the median viremia was 2.09 log copies/mL (range, <0.70-3.34). Cell-associated HIV-1 RNA and DNA were detectable in blood and LNs of all patients. The median cell-associated RNA and DNA were 2.16 log copies/106 cells and 2.60 log copies/106 cells in blood versus 4.31 log RNA copies/106 cells and 3.26 log DNA copies/106 cells in LNs. Regression analysis shows that, in treated patients with sustained low viremia, cell-associated RNA and DNA in blood are better predictors of virus load in LNs than viremia.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Radical surgery for endometriosis.

Infiltrative endometriosis is an uncommon condition that may involve all pelvic organs and is associated with considerable morbidity. A small percentage of patients will have disease that is unresponsive to hormonal therapy and is unsuitable for conservative surgery. Presented is a review of 5 case reports of patients who required radical surgery for control of symptoms caused by endometriosis. Radical surgery was associated with minimal morbidity and a high rate of resolution of symptoms. Radical surgery should be considered as part of the treatment strategy particularly when there is evidence of endometriosis invading into the adjacent gastrointestinal tract or urinary tract.

Adult↗
PubMed1999

Primary HIV infection.

Acute human immunodeficiency virus (HIV) infection, referred to as primary HIV infection (PHI), is associated in the majority of patients with an acute retroviral syndrome presenting similarities with infectious mononucleosis and an exponential rise in viral titres. Symptoms rapidly amend and viraemia levels decline spontaneously to reach a set point at 6 months. The intensity of the acute retroviral syndrome and viraemia levels at set point are predictive of HIV disease progression. There are a number of arguments favouring initiation of treatment at the time of PHI (homogeneity of viral populations, preservation of the immune system, prevention of virus spreading) but these arguments should be weighted against parameters more difficult to evaluate such as long-term drug-associated toxicities and adherence. In clinical practice, adherence is closely linked to the patient's commitment, which is the key parameter for treatment decision.

Acute Disease↗
PubMed1998

Prevalence and incidence rate of HIV, hepatitis B and C among drug users on methadone maintenance treatment in Geneva between 1988 and 1995.

OBJECTIVES: To evaluate the prevalence and incidence rates of infection with HIV, hepatitis B (HBV) and hepatitis C (HCV), in a cohort of drug users (DU) in Geneva, Switzerland. DESIGN: Prospective open cohort study. SETTING: Private methadone maintenance treatment (MMT) programme. PATIENTS, PARTICIPANTS: Over 700 DU in treatment between 1988 and 1995 were tested biannually for HIV, HBV and HCV infection. INTERVENTION: None. MAIN OUTCOME MEASURE: Prevalence for HIV, HBV and HCV at study entry, determined by gender, by injection behaviour, by year of start of MMT and incidence rates for HIV, HBV and HCV, assuming equal risk of seroconversion on each day of the interval between last negative and first positive test. RESULTS: The prevalence at entry into treatment declined dramatically over time for all three viruses. Comparing DU entering treatment before 1988 to those entering treatment after 1993, the prevalence of HIV was 38.2% versus 4.5%, of HBV 80.5% versus 20.1%, and of HCV 91.6% versus 29.8%, respectively. Follow-up rate was 80%. The incidence rates for HIV and HBV were 0.6% and 2.1% per person-year of follow-up, respectively. For HCV the rate was higher (4.2%) especially among women (9.6%). CONCLUSION: These data suggest that DU have changed HIV risk-taking behaviour in response to HIV prevention campaigns. Current prevention efforts should focus on improvement of HCV prevention, identification of high-risk individuals and maintaining safe behaviour.

Cohort Studies↗
PubMed1998

The dental management of patients with natural rubber latex allergy.

Reports of allergic reactions to natural rubber latex have increased during the past two decades with both dental personnel and patients being affected. A dental management protocol is outlined for patients who have latex allergy. This includes: the identification of patients at high risk for developing latex allergy; the creation of a controlled, 'latex free' environment in the dental surgery; and the provision of emergency drugs and equipment that are free from natural rubber latex and may be required for the management of an allergic reaction.

Clinical Protocols↗