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Biomedical subjects

Stephen Taylor

Publications and source records attributed to Stephen Taylor.

24 records · Page 2Linked to original sources

Minimal variation in T-20 binding domain of different HIV-1 subtypes from antiretroviral-naive and -experienced patients.

In-vitro differences in T-20 susceptibility among HIV-1 subtypes have been reported. We therefore studied the T-20 binding domain of a variety of virus subtypes from both antiretroviral-naive and -experienced patients. Minimal variation in the HR-1 region of gp41 was observed, especially within the region responsible for T-20 resistance. Any subtype differences in T-20 susceptibility do not appear to be related to HR-1 genetic variation.

Anti-HIV Agents↗

The effects of antiretroviral therapy on HIV-1 RNA loads in seminal plasma in HIV-positive patients with and without urethritis.

BACKGROUND: High seminal plasma HIV-1 RNA loads (SVL) have been reported during gonococcal, non-gonococcal and chlamydial urethritis in patients not taking antiretroviral therapy. OBJECTIVE: To examine if urethritis leads to increased SVL in HIV-positive patients taking antiretroviral therapy. METHODS: Men who had been taking therapy for at least 3 months were recruited: 24 had urethitis (PWU) and 16 were without urethritis (controls). At three visits, 1 week apart, blood plasma viral load (BVL) and SVL were assayed by quantitative polymerase chain reaction or the NASBA assay. RESULTS: Most subjects had undetectable SVL (18 PWU, 13 controls). Among those with undetectable BVL prior to first study visit, virus was undetectable in semen in 5/5 episodes of chlamydial urethritis, 6/7 episodes of non-gonococcal urethritis and 4/5 cases of gonococcal urethritis. Two PWU with undetectable BVL just prior to the first study visit had low to moderate SVL, which became undetectable by visit 2 following treatment. Of nine subjects with detectable SVL, eight had detectable BVL (3/3 controls and 5/6 PWU). Of these, 1/3 controls and 4/5 PWU (all with gonococcal urethritis) had poorly controlled BVL just prior to the first study visit. These four PWU had high SVL and one had higher levels in semen than in blood. This patient's SVL was reduced more than 20-fold following treatment for gonococcal urethritis. CONCLUSIONS: Effective antiretroviral therapy appeared to limit the effect of urethritis on SVL. When BVL was poorly controlled by antiretroviral therapy, high SVL occurred during gonococcal urethritis, increasing the potential risk of transmitting both wild type and drug resistant strains of HIV-1.

Adult↗

Analysis of HIV-1 variation in blood and semen during treatment and treatment interruption.

The variability of populations of human immunodeficiency virus type 1 (HIV-1) in blood and semen, with respect to envelope and polymerase gene sequences, was examined longitudinally in a patient experiencing treatment failure, interruption of treatment, and successful reintroduction of therapy. During treatment failure, there was little evidence of compartmentalisation between blood and semen, with virus with identical resistance-associated mutations observed in both compartments and lack of clustering with respect to envelope gene sequences. After cessation of treatment, wild-type virus became the predominant population, displaying distinct envelope gene populations, indicating that wild-type virus had overgrown the resistant virus, rather than the resistant virus reverting to wild-type. Once successful therapy had been recommenced, it was possible to distinguish distinct populations of virus in the two compartments. These data support the hypothesis that the male genital tract represents a distinct HIV-1 reservoir.

Adult↗

Pharmacokinetics and pharmacodynamics of drug interactions involving HIV-1 protease inhibitors.

Therapeutic agents used to inhibit the HIV-1 protease are integral to the effective suppression of HIV virus replication by use of synergistic combination therapy. This is inherently dependent on the achievement of effective plasma concentrations of the drug in its active form, and sustaining such levels for the duration of a dosing interval without exceeding thresholds of toxicity. The issues determining the absorption, biotransformation, distribution to and activity at the intended site, and elimination, are myriad and complex. Studies at molecular, cell, and tissue levels are useful for predicting the possible fate of these agents at in vivo, but the wide interindividual variability shown in whole-body pharmacokinetic studies is illustrative of the difficulty in making general statements rather than more guarded recommendations. This paper summarizes the current state of understanding of the major interactions between protease inhibitors themselves and other important commonly used agents in the management of HIV disease, based on data from clinical pharmacokinetic studies.

Cytochrome P-450 Enzyme System↗