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Biomedical subjects

G Collin

Publications and source records attributed to G Collin.

At least 37 records · Page 2Linked to original sources
PubMed2000

Mechanisms of virologic failure in previously untreated HIV-infected patients from a trial of induction-maintenance therapy. Trilège (Agence Nationale de Recherches sur le SIDA 072) Study Team).

CONTEXT: In the Trilège trial, following induction with a zidovudine, lamivudine, and indinavir regimen, human immunodeficiency virus (HIV) replication was less suppressed by 2-drug maintenance therapy than by triple-drug therapy. OBJECTIVE: To identify mechanisms of virologic failure in the 3 arms of the Trilège trial. DESIGN: Case-control study conducted from February to October 1998. SETTING: Three urban hospitals in Paris, France. PATIENTS: Fifty-eight case patients with virologic failure (HIV RNA rebound to >500 copies/mL in 2 consecutive samples) randomized to 3 therapy groups: triple drug (zidovudine, lamivudine, and indinavir), 8; zidovudine-lamivudine, 29; and zidovudine-indinavir, 21; the case patients were randomly matched with 58 control patients with sustained viral suppression. MAIN OUTCOME MEASURES: At virologic failure (S1 sample) and 6 weeks later (S2 sample), assessment of protease and reverse transcriptase gene mutations, plasma indinavir level, and degree of viral load rebound; pill count during induction and maintenance periods. RESULTS: Only 1 primary resistance mutation, M184V, was detected in S1 plasma samples from 4 of 6 patients in the triple-drug and in all 22 in the zidovudine-lamivudine therapy groups and in S2 plasma samples from 3 of 6 in the triple-drug and 20 of 21 in the zidovudine-lamivudine groups. Of controls, M184V was detected in 11 of 13 S1 plasma samples and in 10 of 11 S2 plasma samples. Indinavir levels were undetectable in all S1 samples but 2 in 7 triple-drug cases tested and in the expected range in 11 of 18 S1 and 5 of 12 S2 zidovudine-indinavir case plasma samples tested. Maintenance adherence rates were lower for cases vs controls for zidovudine (P = .05) and indinavir (P = .05). Low indinavir levels, lower adherence rates for zidovudine (P = .04) and lamivudine (P = .03), and rebound to near-baseline values suggested adherence as cause of early failure for 4 of 8 triple-drug cases. In the zidovudine-lamivudine arm, for which case and control adherence rates did not differ significantly (P = .96), most failures occurred late with low rebound, suggesting suboptimal drug potency. In the zidovudine-indinavir arm, virologic failures may be related to both mechanisms. CONCLUSIONS: During the maintenance phase early and late virologic failures appeared to be related more to problems of adherence and antiretroviral treatment potency, respectively, than to selection of resistant mutant viruses.

Anti-HIV Agents↗
PubMed2000

Safety of cryopreservation straws for human gametes or embryos: a preliminary study with human immunodeficiency virus-1.

The aim of this preliminary experimental study was to test the stability of cryopreservation straws to human immunodeficiency virus-1 (HIV-1). Three kinds of straws were tested: four polyvinyl chloride (PVC), four polyethylene terephthalate glycol (PETG) and 20 high-security ionomeric resin (IR). The PVC and PETG straws were sealed ultrasonically, and the IR straw by thermosoldering. Each sealed straw was cut in half to produce two demi-straws and then filled with 100 microl of HIV-1-containing supernatant (reverse transcriptase activity: 15 000 c.p.m./50 microl). The unsealed cotton end of PVC and PETG straws and the two halves of the IR straws (cotton and plastic plug ends) were tested. Each demi-straw was two- thirds submerged in RPMI medium at 37 degrees C, and RPMI samples were withdrawn on days 3, 7 and 11. Viral RNA was extracted from the medium and then amplified by reverse transcriptase-polymerase chain reaction (RT-PCR) followed by nested PCR using primers specific to HIV-1 protease. On day 7, no HIV-1 RNA was detected in any of the different samples of medium that had surrounded the unsealed PVC and PETG straws with cotton ends, but three IR specimens were positive. On day 11, PVC and PETG remained negative but HIV-1 RNA was detected in RPMI samples for two more IR demi-straws (n = 5). In conclusion, under these experimental conditions (at 37 degrees C), the unsealed cotton end PVC, PETG and thermosoldered cotton end IR demi-straws appeared to be safe for HIV-1, while IR straws, sealed or unsealed with a plastic plug and with unsealed cotton ends, leaked.

Cryopreservation↗
PubMed1999

Zidovudine resensitization and dual HIV-1 resistance to zidovudine and lamivudine in the delta lamivudine roll-over study.

OBJECTIVE: To study zidovudine resensitization and dual resistance to zidovudine/lamivudine in HIV-1 isolates from nucleoside reverse transcriptase (RT) inhibitor-experienced patients during selective pressure exerted by zidovudine/lamivudine combination therapy. DESIGN AND METHODS: HIV-1 isolates from 29 patients receiving zidovudine/lamivudine combination therapy in the Delta roll-over study were analysed at entry and during a 1 year follow-up period for phenotypic susceptibility to zidovudine and lamivudine in the ANRS PBMC assay. The RT gene from codon 20 to 230 and at codon 333 was analysed by nucleotide sequencing of the corresponding isolates. RESULTS: HIV-1 isolates from 23 of the 29 patients were phenotypically resistant to zidovudine at baseline; 61% of these patients showed significant zidovudine resensitization during follow-up. The zidovudine IC50 value correlated positively with log10 plasma HIV-1 RNA (P = 0.02) and negatively with the CD4 cell count (P = 0.004). Zidovudine resensitization (related to acquisition of the M184V mutation) was transient, with evolution towards dual resistance to zidovudine and lamivudine in 20 of the 29 patients. The phenotype of certain dually resistant isolates coincided with the emergence of multiple mutations in the 5' part of the RT gene. CONCLUSIONS: M184V-mediated zidovudine resensitization of HIV-1 is transient in most patients who are given zidovudine/lamivudine combination therapy when zidovudine resistance has already emerged. The subsequent evolution towards dual phenotypic resistance to zidovudine/lamivudine corresponds to complex genotypic profiles.

Anti-HIV Agents↗
PubMed1998

Line probe assay for detection of human immunodeficiency virus type 1 mutations conferring resistance to nucleoside inhibitors of reverse transcriptase: comparison with sequence analysis.

We compared the line probe assay (LiPA) to sequence analysis for the detection of mutations conferring resistance to nucleoside inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT). Plasma samples from 40 patients who had received zidovudine, dideoxyinosine, and dideoxycytosine, alone or in combination, and who were enrolled in the ALTIS 2 clinical trial (lamivudine [3TC] plus stavudine) were tested at enrollment and at week 24. RT PCR products from plasma were used for LiPA, and DNA was used for sequence analysis. LiPA gave uninterpretable results for 8.5% of the analyzed codons corresponding to 63 samples, mainly for codons 41, 69, and 70. Several minor discrepancies between the two methods occurred, mainly due to the ability of LiPA to detect mixed populations while sequence analyses detect a single homogeneous population. LiPA is suitable for detecting mixed populations and easy to implement in clinical laboratories and might be useful for epidemiological surveys of primary HIV-1 resistance.

Anti-HIV Agents↗
PubMed1998

Human immunodeficiency virus type 1 subtype F reverse transcriptase sequence and drug susceptibility.

We sequenced and phylogenetically analyzed the reverse transcriptase (RT) regions of the pol genes of 14 human immunodeficiency virus type 1 (HIV-1) isolates from Romanian patients, which were classified as subtype F on the basis of env gene structure. The RT sequences showed that the strains clustered phylogenetically and were equidistant from other HIV-1 subtypes as shown by the neighbor-joining and maximum-likelihood methods, allowing us to define HIV-1 subtype F according to the pol classification. The subtype F RT sequences differed from reported group M RT sequences by 10.94% (for nucleotides) and 7.6% (for amino acids). Phenotypic analysis of subtype F susceptibility to three classes of antiretroviral compounds showed an increase in the 50% inhibitory concentration of the tetrahydroimidazo[4,5,1-jk] [1,4]-benzodiazepin-2-(1H)-one and -thione (TIBO) derivate R82913 for one strain which was naturally resistant to this compound. This first report of subtype F pol sequences confirms the perfect correlation between the phylogenetic positions determined by env and pol analyses and suggests that virus variability might influence the efficacy of antiretroviral treatments. This finding warrants a global evaluation of the phenotypic and genotypic susceptibility of HIV-1 subtypes to antiretroviral drugs.

Adult↗
PubMed1997

Susceptibility of human immunodeficiency virus type 1 group O isolates to antiretroviral agents: in vitro phenotypic and genotypic analyses.

We investigated the phenotypic and genotypic susceptibility of 11 human immunodeficiency virus type 1 (HIV-1) group O strains to nucleoside and nonnucleoside reverse transcriptase (RT) inhibitors and protease inhibitors in vitro. Phenotypic susceptibility was determined by using a standardized in vitro assay of RT inhibition, taking into account the replication kinetics of each strain. HIV-1 group M and HIV-2 isolates were used as references. DNA from cocultured peripheral blood mononuclear cells was amplified by using pol-specific group O primers and cloned for sequencing. Group O isolates were highly sensitive to nucleoside inhibitors, but six isolates were naturally highly resistant to all of the nonnucleoside RT inhibitors tested. Phylogenetic analysis of the pol gene showed that these isolates formed a separate cluster within group O, and genotypic analysis revealed a tyrosine-to-cysteine substitution at residue 181. Differences in susceptibility to saquinavir and ritonavir (RTV) were not significant between group O and group M isolates, although the 50% inhibitory concentration of RTV for group O isolates was higher than that for the HIV-1 subtype B strains. The study of HIV-1 group O susceptibility to antiretroviral drugs revealed that the viruses tested had specific phenotypic characteristics contrasting with the group M phenotypic expression.

Amino Acid Sequence↗
PubMed1993

Clinical relevance of trans-rectal ultrasound, biopsy, and serum prostate-specific antigen following external beam radiotherapy for carcinoma of the prostate.

PURPOSE: To correlate the results of routine transrectal ultrasound-guided prostate biopsies with the usual clinical parameters of digital rectal examination, prostate specific antigen and ultrasound in the follow-up of one hundred patients treated with radical radiotherapy for prostate cancer. METHODS AND MATERIALS: Stage distribution of the 100 patients was T1b; 19, T2a: 24, T2b: 36, T3: 20, T4: 1. Median follow-up is 26 months (range 15-48). One hundred forty-one ultrasound-guided biopsies have been performed with four to seven specimens at each examination. Initial biopsy was scheduled 12 months after radiotherapy and repeated every 6 months until negative or until there was clinical or biochemical evidence of recurrence. RESULTS: Negative biopsies were obtained at 12 months (range 9-15) in only 52%. Of 31 patients with a positive first biopsy who have had a second or third examination, 21 converted to negative at 16-29 months (median: 19) (stage T1b: 3, T2a: 6, T2b: 8, T3: 4). All 21 patients had maintained a normal or decreasing prostate specific antigen (PSA). At last review, negative biopsies had been obtained in 74% patients: 79% (15/19) of T1b, 71% (17/24) of T2a, 72%, (26/36) of T2b, and 76% (16/21) of T3/4. No patient with a negative biopsy has had a local recurrence. Transrectal ultrasound alone (sens: 49%, spec: 57%) was no better than rectal exam (sens: 73%, spec: 66%) in predicting a positive post radiotherapy biopsy. Metastatic disease developed in seven patients, 12% (3/26) of those with a positive biopsy and 5% (4/74) of those with a negative biopsy (p < 0.01). All seven presented first with a rising PSA. CONCLUSION: For patients with a positive biopsy 12 to 24 months after radiotherapy, PSA is the best indicator of biologically active tumor. This preliminary analysis indicates that there may be no need to treat patients with a positive biopsy and negative PSA in the absence of clinical recurrence.

Aged↗