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Biomedical subjects

Claire Harris

Publications and source records attributed to Claire Harris.

5 recordsLinked to original sources

No increase in protease resistance and a decrease in reverse transcriptase resistance mutations in primary HIV-1 infection: 1992-2001.

Rates of antiretroviral resistance in recently transmitted virus in Sydney, Australia fluctuated over the past decade, influenced by treatment trends. Current rates of drug resistance are not high in historical terms or compared with those reported. Rates of resistance to reverse transcriptase inhibitors peaked in the mid-1990s, fell dramatically with the introduction of combination therapy and appear to have plateaued at 10-15% over the past 3 years. Primary resistance mutations in the protease gene are still rare.

Acute Disease↗

Rates of transmission of antiretroviral drug resistant strains of HIV-1.

BACKGROUND: It is clear that transmission of drug resistant HIV-1 is possible and occurs regularly. However, there is a lack of clarity concerning the true rate of this transmission in a given population, the impact of combination therapies on this rate, and the contribution of transmitted resistant virus to treatment failure either in an individual or on a population basis. OBJECTIVES: To provide a review of our current understanding of rates of transmission of drug resistant HIV-1 in various populations and to report the results of a study conducted to determine this rate in Sydney, Australia in the years 1992-2000. STUDY DESIGN: A review of the literature combined with a prospective study of antiretroviral drug resistance in 130 individuals who were diagnosed with symptomatic primary infection at St. Vincent's Hospital, Sydney, Australia between 1992 and 2000. Sequencing of reverse transcriptase (RT) and protease (PR) was performed by the TruGene HIV-1 genotyping kit (Visible Genetics Inc.). RESULTS: The results found in the Sydney population contrast with much of the literature. The prevalence of mutations that conferred primary resistance to protease inhibitors (PIs) was only 0.8% at position V82I. Secondary mutations/polymorphisms were seen in the PR at position L10I/V, K20R, M36I, L63P, A71T/V, or V77I in 60%. L63P was the most frequently found mutation (46.3%). The incidence of protease-resistant strains of HIV in primary HIV-1 infection did not change after the introduction of PIs in 1996. The distribution of the most common resistance mutations in the RT was as follows; M41L (8.5%) and T215Y (8.5%) and K70R (4.8%). The frequency of mutations associated with NRTI resistance was significantly lower in the post 1995 samples (43.9 vs. 19.1%, P < 0.05). Moreover, both M41L and K70R, but not T215Y, occurred with significantly decreased frequency in the post 1995 samples. CONCLUSIONS: In contrast to other studies we found no increase in the rate of PR resistance and a decrease in the rate of RT resistance in recently transmitted virus over the period 1992-2000. The reasons for the differences between these results and those reported from elsewhere may relate to treatment regimens used in the transmitting population and may have implications for treatment policies in this country.

Anti-HIV Agents↗

False negative HIV-1 proviral DNA polymerase chain reaction in a patient with primary infection acquired in Thailand.

BACKGROUND: Qualitative HIV-1 proviral DNA PCR tests have three main diagnostic applications. These include direct detection of viral sequences in the pre-seroconversion window period which may be positive up to 8 days prior to the development of HIV specific antibodies; resolution of indeterminate HIV serological tests and in the diagnosis of neonates born to seropositive mothers where maternal antibodies may be detectable for up to 15 months past partum. METHODS: A total of three serial specimens from a single patient following symptomatic primary HIV-1 infection were assessed by commercially available serological assays for antibodies to HIV and HIV-1 antigen and nucleic acid amplification assays for proviral DNA (Amplicor HIV-1 test, Roche Molecular Systems, CA, USA) and RNA (HIV MONITOR ver1.5, Roche Molecular Systems) according to manufacturers recommendations. A subsequent modified PCR protocol for HIV proviral DNA was performed which included modified primers (SK145/SKCC1B) and altered thermal cycling parameters. RESULTS: We describe a case of HIV infection acquired in Thailand by heterosexual transmission, where a commercially available HIV proviral DNA PCR assay remained negative despite a typical evolving serological profile consistent with seroconversion. CONCLUSION: These data support the use of HIV DNA PCR tests only as a second line supplemental test to licensed standard HIV diagnostic testing strategies, and should be used with care in cases where non-B subtype infection is a possibility.

AIDS Serodiagnosis↗

Audit of the diagnosis, assessment, and treatment of osteoporosis in patients with ankylosing spondylitis.

OBJECTIVE: Osteoporosis (OP) is a well recognized complication of ankylosing spondylitis (AS), but there is no clear guidance to its appropriate management. To establish what might be considered as reasonable practice we surveyed the current practice of consultant rheumatologists in the United Kingdom. METHODS: A questionnaire comprising 14 questions relating to the management of OP in AS was sent to 449 British rheumatologists. Three hundred ten (69%) of the 449 questionnaires sent were returned. RESULTS: Only 98 respondents (31.6%) indicated that assessment of OP formed part of their routine management. Dual energy x-ray absorptiometry (DEXA) was the technique of choice for assessing bone mineral density (BMD) for 284 (91.6%). As general treatment, dietary advice was offered by 101 (32.6%) respondents, whereas 306 (98.7%) gave advice on exercise. Two case scenarios were presented and treatment choices recorded. When faced with a patient with osteopenia (-2.5 < T score < -1.0), 168 (54.2%) respondents would prescribe calcium and vitamin D supplements and 66 (21.3%) would prescribe a bisphosphonate. A second scenario featured a man with femoral neck T score of -2.80 and lumbar spine T score of -0.23. In this case 238 (76.8%) respondents would prescribe a bisphosphonate and 99 (31.9%) calcium and vitamin D, with some prescribing both. Thirty-eight (12.3%) would not prescribe calcium and vitamin D or a bisphosphonate. Two hundred twenty-seven (88.3%) rheumatologists indicated that they would repeat the BMD measurement in a patient with OP within 2 years. CONCLUSION: The majority of British rheumatologists do not routinely assess patients with AS for OP. Most would manage OP in AS in a similar way to postmenopausal OP, but many would not. It does not appear to be generally recognized that in AS, spinal BMD as measured by DEXA rises with advancing radiographic changes, so that hip BMD is the measurement of choice. A robust evidence base is required to clarify guidelines for the management of OP in AS.

Absorptiometry, Photon↗

Childhood ENT disorders. When to refer to specialists.

BACKGROUND: Ear, nose and throat (ENT) are among the commonest reasons for attendance in general practice. Acute problems are managed by the general practitioner, but chronic and recurrent conditions are often referred for surgical intervention. Tonsillectomy and insertion of tympanostomy tubes are two of the most frequently performed paediatric surgical procedures in Australia yet rates of admission vary across geographic areas and socioeconomic strata. Referral patterns and criteria for surgery vary widely. OBJECTIVE: This article reviews the natural history of some common childhood ENT conditions and the evidence of effectiveness of traditional surgical interventions in order to address the question: 'When should GPs refer to an ENT surgeon (or conversely, when should they not refer)?' DISCUSSION: Recurrent and chronic ear and throat conditions in children will usually resolve spontaneously. There is no good evidence of long term benefit from surgical interventions for several common ENT conditions. General practitioners need to weigh up the disadvantages and risks of the surgery with the likely benefit to the individual patient.

Acute Disease↗