Anne Mijch

Prevalence of and risk factors for HIV-associated neuropathy in Melbourne, Australia 1993–2006

The aim of the study was to describe the prevalence of and risk factors for HIV‐associated sensory neuropathy (HIV‐SN) in 2006 [the era of stavudine, didanosine and zalcitabine (dNRTI)‐sparing highly active antiretroviral therapy (HAART)] and to compare our findings with data obtained in the same clinic in 1993 (pre‐HAART) and 2001 (frequent use of dNRTI‐containing HAART).

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

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.

Depressive symptoms reduced in individuals with HIV/AIDS treated with highly active antiretroviral therapy: a longitudinal study

Objective: The aims of this study were to investigate the stability of depressive symptoms over time, explore possible reasons for the genesis of depressive symptoms, examine psychosocial adjustment over time and examine the effects of the introduction of highly active antiretroviral therapy (HAART) in a group of HIV infected patients. Method: HIV seropositive outpatients were assessed at 6 monthly intervals over a 2-year period. At each assessment patients completed the Beck Depression Inventory, the Life Event Inventory, the Core Bereavement Item questionnaire and the Psychosocial Adjustment to Illness Scale. Details regarding HIV illness progression and antiretroviral treatment were recorded for each follow-up assessment. Results: One hundred and sixty-three patients completed the baseline assessment and proceeded to the 2-year follow-up study. Most patients remained well over the 2-year follow-up period; mean CD4 count for the group increased over the study period. Ten patients developed AIDS and 18 patients died. Antiretroviral medications changed significantly during the follow-up, with most patients changing to combination (triple) therapy, which included the use of a protease inhibitor. Psychosocial stressors (life event distress and number of bereavements) reduced as the study progressed. Reported depressive symptoms decreased over time and psychosocial adjustment to illness tended to improve over the 2-year period. Conclusions: Over a 2-year follow-up period HIV/AIDS symptoms and illness markers and psychosocial adjustment to illness improved, psychological stressors and depressive symptoms decreased, with a temporal relationship to changes in antiretroviral therapy.

Immune Reconstitution Hepatitis in HIV and Hepatitis B Coinfection, Despite Lamivudine Therapy as Part of HAART

Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) coinfection occurs commonly. The introduction of antiretroviral therapy can result in immune reconstitution hepatitis. We describe 2 coinfected patients who developed clinical flares of HBV disease, despite the inclusion of lamivudine, a drug with anti-HBV activity, in their HAART regimens. Potential strategies to manage individuals with HBV/HIV coinfection are discussed.

Fertility and reproductive choice in women with HIV-1 infection

Objective:To measure fertility and birth rates and to describe the reproductive histories of women diagnosed with HIV-1 infection in Australia. Methods:The medical records of 294 women with HIV-1 infection in four states of Australia were reviewed. Expected fertility and birth rates were calculated using national statistics. Results:In the study population, 152 (52%) women had at least one pregnancy prior or subsequent to HIV-1 diagnosis. At maternal HIV-1 diagnosis, 71 (24%) women had a total of 106 children aged under 15 years. During the study period, 246 women were aged 15–44 years and 58 (23%) of these became pregnant after HIV-1 diagnosis. Women whose exposure to HIV-1 was injecting drug use were twice as likely to become pregnant and more likely to have multiple pregnancies than women who did not report injecting drug use. The annual general fertility rate was 30 per 10 000 compared with 63 per 10 000 for the Australian female population (aged 15–44 years), and the birth rate in women with HIV-1 infection was one-half that of the general female population. Of pregnancies confirmed after HIV-1 diagnosis, 47% were voluntarily terminated, a rate more than double that of the general population. All multiple terminations were among women whose exposure to HIV-1 was injecting drug use. Conclusions:Fertility and birth rates among women with HIV-1 infection are lower than the general population and the rate of termination higher. The results of this study provide a basis for the management of women with HIV-1 infection who are considering pregnancy.

The increased risk of fatal liver disease in renal transplant patients who are hepatitis Be antigen and/or HBV DNA positive.

To determine whether active viral replication is associated with increased morbidity and mortality in chronic carriers of hepatitis B virus (HBV) undergoing renal transplantation, we reviewed 23 years of experience at our hospital. Over the period 1966-1989, 42 chronic carriers of hepatitis B surface antigen (HBsAg) received renal transplants, 32 of whom had functioning grafts for 12 months or longer. Stored sera were tested for markers of hepatitis B virus, hepatitis C virus (HCV), and hepatitis delta virus (HDV) infection, and the serologic findings were correlated with clinical and biochemical data. The presence of HBV DNA and/or hepatitis Be antigen (HBeAg) in serum samples collected prior to transplantation was associated with an increased probability of death from liver disease. Whereas 5 of 10 patients in this group died of chronic liver disease, only 1 of 15 patients who were HBV DNA and/or HBeAg negative prior to transplantation died of liver disease. This difference is highly significant (P less than 0.02). No difference in outcome was attributable to age at transplantation, gender, country of birth, or the presence of abnormal hepatic transaminase levels prior to transplantation.

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.

Depression in People Living with HIV/AIDS Attending Primary Care and Outpatient Clinics

Objective: Our aim was to gain an estimate of the rate of depressive disorder in patients with HIV/AIDS attending general practice and to investigate factors associated with depression. A further objective was to determine the ability of non-mental health medical practitioners to detect depressive symptoms in their patients with HIV/AIDS. Method: Participants comprised 322 persons living with HIV/AIDS ((PLWHA); 13 females, 309 males; mean age 41.4, SD = 8.9) who were recruited from four general practice clinics specializing in HIV medicine and from an infectious diseases clinic. Medical, psychiatric and sociodemographic data were obtained. In addition, participants completed the Inventory to Diagnose Depression (IDD), a self-report measure to detect depression. Results: Twenty-two per cent of the sample met criteria for a current Major Depressive Episode (DSM-IV defined) on the IDD. Overall, there was moderate agreement between treating doctors’ diagnosis of depression and patients’ self-report of depressive symptoms. A multivariate model indicated that being in a current relationship was associated with lowered odds of depression (OR = 0.43; CI = 0.23–0.81). The factors strongly associated with increased odds of depression were a past history of illicit drug use (OR = 2.98; CI = 1.60–5.54) and a diagnosis of ‘stress’ by treating doctors (OR = 5.65; CI = 2.50–12.77). HIV-related medical variables such as immune function, use of antiretroviral medication and duration of HIV infection were not associated with depression. Conclusions: There was a high rate of self-reported depression in this group of PLWHA which was also recognized by treating clinicians. Being in a relationship appeared to afford protection against depression while having a history of illicit drug use and current ‘stress’ were highly associated with depression. Interestingly, HIV-related medical variables including laboratory markers of HIV disease, duration of illness and antiretroviral medication regimen were not related to depression.

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.

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.