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Biomedical subjects

A Mijch

Publications and source records attributed to A Mijch.

At least 19 recordsLinked to original sources
PubMed2006

Virological and immunological outcomes at 3 years after starting antiretroviral therapy with regimens containing non-nucleoside reverse transcriptase inhibitor, protease inhibitor, or both in INITIO: open-label randomised trial.

BACKGROUND: Antiretroviral therapy has greatly reduced HIV mortality and morbidity. However, the best sequence of regimens and implications of initial regimen for long-term therapeutic success are not well defined. METHODS: In INITIO, a large international randomised trial, we compared antiretroviral therapy with two nucleoside analogue reverse transcriptase inhibitors (didanosine+stavudine) plus either a non-nucleoside reverse transcriptase inhibitor (efavirenz, EFV) or a protease inhibitor (nelfinavir, NFV), or both (EFV/NFV), in patients with HIV-1 infection who had not previously received antiretroviral drugs. Primary outcomes were proportion with undetectable HIV RNA in plasma, and change in CD4 count from baseline at 3 years. Analyses were by intention-to-treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN44582462. FINDINGS: We followed up 911 participants (297 EFV, 311 NFV, 303 EFV/NFV). At 3 years, the proportion with HIV RNA less than 50 copies per mL was highest in the EFV group (188 [74%] EFV, 162 [62%] NFV, 155 [62%] EFV/NFV; p=0.004). Mean (95% CI) increases in CD4 count were 316x10(6) cells per L (288-343) for EFV, 289x10(6) cells per L (262-316) for NFV, and 274x10(6) cells per L (231-291) for EFV/NFV (p=0.1). Fewer participants in the EFV group than in the other groups stopped adequate antiretroviral therapy for more than 30 days (p=0.005). Participants in the EFV/NFV group had shorter time to stopping the initial regimen (p<0.0001) and to a treatment modifying adverse event (p=0.04) than those in the other groups. INTERPRETATION: Starting antiretroviral therapy with a three-drug/two-class regimen including efavirenz was better than starting with regimens including nelfinavir or efavirenz plus nelfinavir in terms of virological suppression and durability of the initial regimen. The shorter time on adequate antiretroviral therapy or to a treatment-modifying adverse event might explain the absence of additional benefit for the four-drug regimen.

Acquired Immunodeficiency Syndrome↗
PubMed2006

A randomised controlled trial of omega-3 fatty acid supplementation for the treatment of hypertriglyceridemia in HIV-infected males on highly active antiretroviral therapy.

BACKGROUND: Hypertriglyceridaemia is a recognised metabolic abnormality in HIV-infected people, increasing in severity in people treated with highly active antiretroviral therapy (HAART). An alternative treatment for hypertriglyceridaemia in non-HIV-infected populations is omega-3 fatty acid supplementation. This study aimed to compare the effectiveness of omega-3 fatty acid supplementation and placebo in lowering fasting triglyceride levels in HIV-infected patients on HAART. METHODS: A placebo-controlled, randomised, double-blind trial in participants on stable HAART with fasting triglycerides of >3.5 mm to 10.0 mm using 9 g of omega-3 fatty acids versus placebo (olive oil) after a 6-week lead in on dietary therapy. RESULTS: Eleven patients were enrolled. The mean triglyceride level for the population decreased from 5.02 mm at baseline to 4.44 mm (-11.6%) after dietary intervention and 3.37 mm (-32.9%) after the 8-week treatment period. In the omega-3 fatty acid arm of the study, triglycerides fell from 5.34 mm to 5.02 mm (-6%) after dietary intervention and to 2.30 mm (-56.9%) after the treatment period. In the placebo arm of the study, triglycerides fell from 4.77 mm to 4.05 mm (-15.1%) after dietary intervention and to 4.08 mm (-14.5%) after the treatment period. Using the random effects model, a statistically significant effect on triglycerides of omega-3 fatty acid versus placebo was found (chi(2) = 6.04, P = 0.0487). The estimated difference between groups for change in mean triglycerides over 8 weeks was -2.32 mm (95% CI -4.52, -0.12 mm). CONCLUSIONS: Omega-3 fatty acids are likely to be an effective treatment for hypertriglyceridaemia in HIV-infected males on HAART.

Adult↗
PubMed2006

Depression and neurocognitive performance in individuals with HIV/AIDS: 2-year follow-up.

OBJECTIVES: The aims of this study were to follow a cohort of HIV-infected individuals for 2 years to assess changes in depression and neuropsychological performance over time, to explore the relationship between depression, HIV illness and neuropsychological performance, and to examine the natural history of the effect of highly active antiretroviral therapy (HAART) on depression and neurocognitive performance. METHODS: HIV-seropositive out-patients were assessed at baseline and at 2-year follow-up. At each assessment, patients were assessed for depression [using the Beck Depression Inventory (BDI) and Structured Clinical Interview (SCID-CV)] and completed a battery of neuropsychological tests including the Cambridge Neuropsychological Test Automated Battery (CANTAB) and the Hopkins HIV Dementia Scale (HDS). RESULTS: At baseline, 34.8% scored > or =14 on the BDI [> or =14 suggests depressive symptoms (DS)]. The SCID-CV revealed that 27% of participants met the criteria for current mood disorder. Seven per cent of the participants' scores on the HDS indicated HIV-associated cognitive changes. Eighty participants were re-tested at 2-year follow-up and were split into two groups based on BDI scores at baseline. CANTAB results revealed that the cohort were significantly impaired on nine of 10 measures compared with age-matched normative data. Neurocognitive performance significantly improved for participants with no DS at baseline, whereas participants with DS at baseline did not show as much improvement. Multivariate analysis revealed that 40% of the change in cognitive performance was attributable to the variables age, AIDS and HAART regimen. CONCLUSION: These results suggest a significant decline in depression scores and an improvement in several neurocognitive domains over time, with a relationship between HIV illness, HAART, symptoms of depression and neurocognitive performance.

Acquired Immunodeficiency Syndrome↗
PubMed2006

Increased health care utilization and increased antiretroviral use in HIV-infected individuals with mental health disorders.

OBJECTIVES: The aims of the study were to describe the prevalence and associations of mental health disorder (MHD) among a cohort of HIV-infected patients attending the Victorian HIV/AIDS Service between 1984 and 2000, and to examine whether antiretroviral therapy use or mortality was influenced by MHD (defined as a record of service provision by psychiatric services on the Victorian Psychiatric Case Register). It was hypothesized that HIV-positive individuals with MHD would have poorer treatment outcomes, reduced responses to highly active antiretroviral therapy (HAART) and increased mortality compared with those without MHD. METHODS: This is a retrospective cohort of 2981 individuals (73% of the Victorian population diagnosed with HIV infection) captured on an HIV database which was electronically matched with the public Victorian Psychiatric Case Register (VPCR) (accounting for 95% of public system psychiatry service provision). The prevalence, dates and recorded specifics of mental health disorders at the time of the electronic match on 1 June 2000 are described. The association with recorded MHD, gender, age, AIDS illness, HIV exposure category, duration and type of antiviral therapy, treatment era (prior to 1986, post-1987 and pre-HAART, and post-HAART) on hospitalization and mortality at 1 September 2001 was assessed. RESULTS: Five hundred and twenty-five individuals (17.6% of the Victorian HIV-positive population) were recorded with MHD, most frequently coded as attributable to substance dependence/abuse or affective disorder. MHD was diagnosed prior to HIV in 33% and, of those diagnosed after HIV, 93.8% were recorded more than 1 year after the HIV diagnosis. Schizophrenia was recorded in 6% of the population with MHD. Hospitalizations for both psychiatric and nonpsychiatric illness were more frequent in those with MHD (relative risk 5.4; 95% confidence interval 3.7, 8.2). The total number of antiretrovirals used (median 6.4 agents vs 5.5 agents) was greater in those with MHD. When adjusted for antiretroviral treatment era, HIV exposure category, CD4 cell count and antiretroviral therapy, survival was not affected by MHD. CONCLUSIONS: MHD is frequent in this population with HIV infection and is associated with increased healthcare utilization but not with reduced survival.

Adult↗
PubMed2006

Cohort analysis of two multidisciplined adherence intervention programmes for patients on antiretroviral therapy.

The aim was to analyse data from two randomized controlled trials (RCTs) to determine if an adherence intervention programme for antiretroviral therapy (ART) resulted in a reduction in viral load. A cohort analysis of pre- and post-intervention viral loads and CD4 counts using paired analysis was undertaken on participants who received the intervention programme. Analysis was also undertaken on a control group. The intervention participants had an increase in mean CD4 count (450-478, P = 0.26), and a decline in log viral load (2.48-2.36, P = 0.056). The control group had a decline in mean CD4 counts (596-570, P = 0.53), and an increase in log viral load (2.09-2.11, P = 0.78). The use of an adherence intervention programme is associated with a decrease in mean viral load, which is in contrast to the control group that demonstrated an increase in viral load over time.

Antiretroviral Therapy, Highly Active↗
PubMed2005

Breast milk pasteurisation in developed countries to reduce HIV transmission. Do the benefits outweigh the risks?

BACKGROUND: Transmission of HIV through breastfeeding is well documented. The World Health Organisation advise HIV-infected women in developed countries to use alternatives to breastfeeding together with highly active antiretroviral therapy and optimal management of delivery to prevent transmission of HIV to their infant. CASE REPORT: We present the case of an HIV-infected woman electing to exclusively breastfeed for six months and applying milk pasteurisation techniques without transmission to her infant. Two paired samples of her breast milk were tested for HIV RNA prior to and after pasteurisation. The first pair of specimens reported no change in HIV RNA copy number, the second pair of specimens reported an increase in copy number. DISCUSSION: This technique, the evidence for HIV inactivation and the effects pasteurisation has on nutritional and immunological components of breast milk are discussed. CONCLUSION: In conclusion, we believe there is currently insufficient data to recommend this technique either as a safe alternative to formula feeding in resource-rich countries or as a method for providing intact immunological components of breast milk to the infant.

Acquired Immunodeficiency Syndrome↗
PubMed2004

Multidisciplinary HIV adherence intervention: a randomized study.

Maintaining greater than 95% adherence to antiretroviral medication is necessary in order to have the greatest therapeutic impact on HIV infection. Furthermore, evidence suggests that adherence rates of between 70% and 89% are significantly associated with viral rebound and the development of drug resistance. Adherence rates at and above the 95% level are difficult for patients to achieve and maintain. Our aim was to determine if an adherence intervention could improve adherence among patients attending an ambulatory care clinic at a large public hospital. The intervention was delivered by a multidisciplinary team of health care professionals and consisted of education coupled with the provision of devices designed to assist patient memory and adherence. A crucial component of the intervention consisted of the identification of patient specific barriers to adherence and the development of strategies to circumvent these problems. Adherence was assessed using patient self-report over the past 4, 7, and 28 days and by calculation of the Morisky score. The study was conducted as a randomised controlled trial using the stepped wedge design with a total of 68 subjects randomised to receive the intervention over a 20-week period. Adherence before and after the intervention formed the analysis. There was a significant decrease in the number of missed doses over the past 4 (1.9 to 1.0, p < 0.001), 7 (3.0 to 1.8, p < 0.001) and 28 (7.4 to 4.2, p < 0.001) days and a decrease in the Morisky score, indicating an improvement in medication taking behaviour (1.3 to 0.5 p < 0.001).

Adult↗
PubMed2003

Randomized trial of an adherence programme for clients with HIV.

Our aim was to determine if a comprehensive adherence package improved self reported adherence to antiretroviral therapy. The adherence package included an education programme, individualized planning of regimens, and the opportunity for a patient to choose from a number of adherence aids and reminder devices. A randomized step wedge design was used. Forty-three individuals were randomized to begin the intervention over a five-month period. There was a substantial fall in the number of missed doses reported for the last four days (0.76 to 0.38, P =0.03) and last seven days (1.5 to 0.74, P =0.005) but not for the last 28 days (2.5 to 2.5, P =0.63). There was no statistical difference in the viral load or CD4 lymphocyte count in the period before or after the intervention. The Morisky score during the pre and post intervention periods was significantly different (P =0.006), 2.9 (SD 0.9) and 3.3 (SD 0.8) respectively. This adherence package improved self reported adherence during the last four and seven days.

Adult↗
PubMed2001

Comparison of genotyping and phenotyping methods for determining susceptibility of HIV-1 to antiretroviral drugs.

OBJECTIVE(S): To compare antiretroviral resistance susceptibility testing of patient HIV-1 strains using genotype and phenotype methods. DESIGN: Eighteen plasma samples with viral load > 2000 HIV-1 RNA copies/ml were randomly selected for testing by both methods. Disease and treatment data were available for all patients. METHODS: Samples were analysed genotypically using a kit assay (HIV-1 Genotyping Systems, Applied Biosystems), performed by the Clinical Research Laboratory at Macfarlane Burnet Centre for Medical Research. Samples were analysed phenotypically using a rapid phenotypic assay (PhenoSenseTM HIV, ViroLogic), performed by the manufacturer. Results from both methods were interpreted using a defined protocol. Each susceptibility assay was performed and interpreted by individuals unaware of either the clinical data or the results of the other susceptibility assay. Concordance was defined categorically as either the presence of reduced susceptibility (> 2.5-fold change) in the phenotypic assay and resistance associated mutations in the genotypic assay, or the absence of these findings in both assays. RESULTS: Concordance between phenotypic and genotypic susceptibility testing was 81% for nucleoside reverse transcriptase inhibitors, 91% for non-nucleoside reverse transcriptase inhibitors and 90% for protease inhibitors. Complete concordance between phenotype and genotype for all 14 drugs evaluated was observed in three (17%) patient samples. CONCLUSIONS: Phenotypic and genotypic susceptibility appear to provide similar results. However, interpretation of genotypic results can be complicated, and both methods still require clinical validation.

Anti-HIV Agents↗
PubMed2001

"Helicobacter rappini" isolates from 2 homosexual men.

We report 2 cases of bacteremia due to "Helicobacter rappini" in 2 young, homosexual men, including the first report of H. rappini in a human immunodeficiency virus-positive patient. Blood cultures showed a spiral, fusiform, gram-negative bacterium with bipolar sheathed flagella.

AIDS-Related Opportunistic Infections↗
PubMed2001

Quantification of mitochondrial DNA in peripheral blood mononuclear cells and subcutaneous fat using real-time polymerase chain reaction.

BACKGROUND: With decreased rates of HIV mortality and disease progression attributable to treatment with nucleoside analogue reverse transcriptase inhibitors (NRTIs), attention has now become focused on the toxicities of these forms of treatment. It is believed NRTIs cause a decrease in mitochondrial DNA (mtDNA) synthesis due to their inhibition of DNA polymerase gamma. This hypothesis is supported by in vitro data from muscle biopsies and human lymphoblastic cell lines. The resulting mitochondrial toxicity is thought to manifest itself in a variety of clinical symptoms including fatigue, fat wasting and peripheral neuropathy. A non-invasive test of mitochondrial toxicity is needed to assess toxicity and optimise HIV treatment strategies. Peripheral blood mononuclear cells (PBMC) and subcutaneous fat could be ideal and accessible sources of mtDNA for examining toxicity. OBJECTIVES: The objectives of this study were (a) to develop an assay to quantify the mtDNA copy number of PBMC and obtain reproducible results and (b) to establish the utility of subcutaneous fat as a source of mtDNA for quantification. STUDY DESIGN: PBMC were isolated from blood by centrifugation over Ficoll-Paque and subcutaneous fat was obtained from two 3 mm punch skin biopsies. Following DNA extraction, the mtDNA copy number in each sample was quantified by real-time polymerase chain reaction (PCR). RESULTS: The real-time PCR assay was found to generate consistent and reproducible results with replicates of samples undertaken within the same run, and in two or more different runs, having a mean coefficient of variation of 11.3 and 17.2%, respectively. PBMC and subcutaneous fat contained 409+/-148 and 2042+/-391 copies of mtDNA per cell, respectively. CONCLUSIONS: From the work carried out it can be concluded that firstly, the real-time PCR assay generates consistent and reproducible results, and secondly that mtDNA can be extracted and quantified from PBMC and subcutaneous fat.

Adipose Tissue↗
PubMed2001

Suicidal behaviour in people with HIV/AIDS: a review.

OBJECTIVE: To review the existing literature on suicidal behaviour in people with HIV/AIDS infection. METHOD: A search on the Index Medicus/MEDLINE database was performed, for articles that investigated and/or reviewed suicidal behaviour in people with HIV at any stage of the illness. Only articles written in English were used in this review. RESULTS: Most studies have been done on homosexual/bisexual groups, with little data available for heterosexual populations or women. Studies show an increased rate of suicidal ideation, suicide attempts and completed suicide in individuals with HIV/AIDS. Of note, there is a high prevalence of psychiatric illness and substance abuse in those with suicidal behaviour. CONCLUSIONS: The increased rate of suicidal behaviour in HIV-infected persons is consistent with findings in other medically ill groups with chronic, life-threatening disorders. However, assessment of any possible direct effect of HIV/AIDS on suicidal behaviour is confounded by methodological limitations of many of the studies. More longitudinal studies encompassing other affected groups including heterosexual populations and women are needed to elucidate the relationship between suicidal behaviour and HIV/AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Nocardia infection in heart-lung transplant recipients at Alfred Hospital, Melbourne, Australia, 1989-1998.

Nocardia infections are uncommon in recipients of heart, lung, or heart-lung transplants, but such infections are well described. Frequent episodes of rejection, high-dose prednisolone treatment, renal impairment, and prolonged respiratory support have all been shown to increase the risk of Nocardia infection in this group. In this retrospective review of 540 recipients of heart, lung, or heart-lung transplants, 10 patients developed Nocardia infection (frequency, 1.85%). Infection occurred at a mean +/- standard deviation of 13+/-14.5 months after transplantation. All patients had pulmonary disease with no evidence of extrapulmonary disease. The Nocardia infection did not contribute directly to patient deaths. Coinfection with other pathogens was present in 6 patients, and 2 patients had sequential infections. Radiological findings varied. All isolates were susceptible to trimethoprim-sulfamethoxazole, amikacin, and imipenem. Treatment regimens varied. Two (30%) of 6 patients treated with trimethoprim-sulfamethoxazole developed adverse reactions, which necessitated a change in antibiotic therapy. The optimal treatment regimen, which comprises both the antimicrobial agent and the length of treatment, is unclear.

Adult↗