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

OBJECTIVES: 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). METHODS: This was a cross-sectional comparative study using convenience sampling. HIV-positive adults attending a tertiary referral clinic over a 2-week period were screened for HIV-SN using the AIDS Clinical Trials Group screening tool. HIV-SN was defined as present if the patient had both neuropathic symptoms and abnormal signs. Demographic, clinical, laboratory and treatment data were considered as possible risk factors for HIV-SN, and results were compared with data obtained in the same clinic in 1993 and 2001. RESULTS: One hundred patients were screened. The prevalence of HIV-SN was 42%, which was unchanged since 2001 (44%) despite a significant reduction in the use of dNRTIs. HIV-SN remained much more common than in 1993 (42% vs 13%; P<0.0001). The only independent associations with HIV-SN in 2006 were increasing patient age and a history of exposure to either stavudine or indinavir. This compares with 1993 when neuropathy was increased in those with Mycobacterium avium complex infection, and 2001 when patient age and use of stavudine and didanosine were the independent associations with HIV-SN in this clinic. CONCLUSIONS: HIV-SN remained common among ambulatory patients in 2006 (42% prevalence) despite a significant reduction in the use of dNRTIs. In addition to patient age and stavudine exposure, indinavir use may be a risk factor for HIV-SN.

Successful control of disseminated Scedosporium prolificans infection with a combination of voriconazole and terbinafine.

Disseminated Scedosporium prolificans infections are almost uniformly fatal because of their resistance to antifungal agents. Recently, synergy between triazoles and terbinafine has been demonstrated against Scedosporium prolificans in vitro. Reported here is a patient who developed disseminated Scedosporium prolificans infection following bone marrow transplantation and who was successfully treated with a combination of voriconazole and terbinafine in addition to aggressive surgical debridement. Antifungal synergy testing and combination therapy should be considered in cases of disseminated infection with Scedosporium prolificans.

The prevalence of lipodystrophy in an ambulant HIV-infected population: it all depends on the definition.

OBJECTIVES: This study's objective was to determine the prevalence of body shape changes and metabolic abnormalities in an ambulant population with HIV infection. Three different definitions of lipodystrophy were used to assess these changes. Patients' anthropometric measures and dual-energy X-ray absorptiometry (DEXA) scans were compared in order to estimate fat distribution in this population. We sought to evaluate potential predictors for lipodystrophy according to each of the three definitions. METHODS: We performed a cross-sectional study in the outpatient clinic of a tertiary referral hospital in Melbourne, Australia. We enrolled a total of 167 HIV-infected ambulatory patients over 3 months in mid-1998. Data on 159 males, 149 of whom were receiving triple combination antiretroviral therapy, were evaluated. Anthropometric measures, clinical examination, self-report of body shape changes, biochemical measures and DEXA scan were used to assess lipodystrophy and risk factors for cardiovascular disease. Patients described body shape changes in the face, trunk, arms and legs. Laboratory parameters measured included fasting triglyceride (TG), cholesterol, high-density lipoproteins (HDL), glucose, insulin, CD4 cell count and plasma HIV RNA. Current and past antiretroviral therapies were ascertained. RESULTS: According to one proposed Australian national definition of lipodystrophy (LDNC), the prevalence of lipodystrophy in this population was 65%. This definition included an objective assessment with major and minor criteria. Patient-defined lipodystrophy (LDP), which involved a subjective assessment of thinning arms and legs and central adiposity, occurred in 19%. Patient-defined lipoatrophy (LAP), which involved a subjective assessment of thinning arms and legs without central adiposity, occurred in 21.3%. No change in body habitus was noted by 37% of the cohort. Hypercholesterolaemia was recorded in 44%, hypertriglyceridaemia in 52% and elevated insulin levels in 23%. Anthropometry was predictive of the per cent total body fat recorded by DEXA scan, but produced consistently lower values. In multivariate analysis, LDP and LAP were significantly associated with stavudine (d4T) use, while LAP was also associated with zidovudine (ZDV) treatment. There were no treatment associations with LDNC. Protease inhibitor (PI) exposure was associated with metabolic changes but not patient perceived body shape changes, while d4T and ZDV exposure was associated with increased triglycerides and reduced peripheral fat stores. CONCLUSIONS: The prevalence of body shape changes in a single population varied depending on the definition applied. The LDNC definition overestimated body shape abnormalities in comparison with patient perception. LAP was associated with significantly lower fat stores measured by anthropometry and DEXA scan than those identified under the LDNC definition. In contrast to LDNC, LAP was associated with d4T exposure, nucleoside reverse transcriptase inhibitor (NRTI) and ZDV duration of use, but not PI use. Until a consensus definition for lipodystrophy is developed, including agreement on objective measurement and thresholds for abnormality, careful description of the individual components of the syndrome is required to enable cohort comparisons so that predictors of the syndrome can be assessed more accurately and outcome studies made feasible.

Does plasma HIV RNA predict outcome in a cohort of treated HIV-infected individuals followed over 3 years?

BACKGROUND: Despite reductions in AIDS illness and mortality, it is increasingly apparent that a significant proportion of individuals treated with combination antiretroviral (cARV) therapy have continuing or recrudescent HIV RNA in plasma. The predictive value of plasma HIV RNA in treated individual remains uncertain and rates of and risk factors for adverse outcomes such as hospitalisation, opportunistic infections and deaths are needed. OBJECTIVES: The objectives of this study were to establish a retrospective cohort of individuals treated with cARVs, to assess factors associated with detectable HIV RNA and to determine rates of and risk factors for hospitalisation, opportunistic infection and mortality over 3 years of follow-up. STUDY DESIGN: All individuals treated at The Alfred Hospital, Melbourne, Victoria between January and June 1997 who had had plasma HIV RNA measured were included in the retrospective cohort. Clinical, virological and hospitalisation data were recorded and validated by cross-reference with electronically stored laboratory, hospital activity and state notification databases. Outcome was assessed at October 2000. RESULTS: Amongst the 555 individuals tested, 438 (60.7%) had detectable (>500 copies/ml) HIV RNA (bDNA assay, version 2) at baseline. The overall mortality rate was 5.5 per 100 person years; the AIDS rate 1.99 per 100 person years and hospitalisation rate 16.4 per 100 person years. Risk factors for death in this population identified by univariate analysis were HIV RNA concentration at baseline and at follow-up October 2000, nadir and most recent CD4 lymphocyte number, not receiving cARV as initial treatment, total number of ARV agents and number of changes in ARV per year, developing AIDS and being hospitalised during follow-up. In a multivariate model, the most recent CD4 lymphocyte number, the number of different ARVs per year and having more than one hospitalisation remained predictive of death. CONCLUSIONS: HIV RNA remained detectable in the majority (60.7%) of this treatment-experienced population over 3 years, yet mortality rate remained relatively low at 5.5 per 100 person years. Factors associated with death were immunological (CD4 lymphocyte number) and treatment related (numbers of changes of ARV and hospitalisation) rather than virological (HIV RNA) in this cohort. We believe hospitalisation rates may be a useful marker of HIV disease in cARV treated populations and may identify groups at risk of poorer outcome and in need of intervention.

Psychosocial factors are associated with prolonged hospitalization in a population with advanced HIV.

Our aim was to define a subgroup of patients with HIV at risk of adverse outcomes in terms of psychosocial factors in order to improve the targeting of hospital resources. The International Classification of Diseases, 9th Revision (ICD-9) coded discharges of all inpatients with HIV discharged from a tertiary hospital between July 1996 and March 1999 were matched against variables in the HIV/AIDS database. A 'prolonged hospitalization' subgroup was defined as those patients whose cumulative length of stay exceeded 90 days in the 33-month period. There were 2778 non-day stay discharges (n=757 patients) constituting 21,286 bed-days. The prolonged hospitalization group (n=62) accounted for 44.3% of the bed-days. Psychosocial co-diagnoses were associated with prolonged hospitalization in both crude and adjusted logistic analyses. These included psychiatric diagnoses such as mania, psychosis and anxiety, HIV dementia, housing issues and the need for social work interventions. In conclusion, a small group of individuals at risk of adverse outcomes has been defined by markers of psychosocial dysfunction. Increased understanding of this group should enable the development of programmes directed at morbidity and mortality.

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.

Secondary mania in patients with HIV infection: are antiretrovirals protective?

A case-control study of 19 patients with HIV-associated mania and 57 HIV-seropositive control patients matched by CD4 cell count, age, and year of treatment was undertaken to investigate associations with risk factors for human immunodeficiency virus (HIV) infection, treatment, and disease. There was no significant difference between groups for HIV exposure category, baseline health status, or drugs other than antiretrovirals. Zidovudine therapy provided a significant protective effect against the development of mania, whether administered at or prior to diagnosis of mania. In a 3-year follow-up study, incident AIDS dementia was significantly more common in patients with mania, despite no apparent difference in survival between cases and controls. These findings strengthen the evidence of an etiological association of HIV neuropathology with AIDS mania by demonstrating a protective effect of an antiretroviral agent able to penetrate the central nervous system.

Secondary mania in patients with HIV infection.

OBJECTIVE: The aim of this study was to identify a cohort of patients with mania secondary to HIV infection, to describe the clinical and radiological features of HIV-related mania, and to describe the treatment outcome of the patients. METHOD: All patients referred to the HIV consultation-liaison psychiatry service over the 29-month period from January 1993 to June 1995 were screened for the presence of manic symptoms. Diagnosis of mania was made according to DSM-III-R. Cases were defined as secondary mania if there was no clear history of mood disorder, and no family history of mood disorder. Cases were interviewed by the treating psychiatry registrar and psychiatrist to obtain information regarding present and past psychiatric history and family history of psychiatric disorder. The psychiatry registrar and consultant determined treatment. RESULTS: Twenty-three patients with mania were identified; 19 were considered to have secondary mania. The prevalence of secondary mania over the 29 months was 1.2% for HIV-positive patients, and 4.3% for those with AIDS. The clinical characteristics and response to treatment appeared to be similar to mania associated with bipolar affective disorder (primary mania). Neuroradiological abnormalities were common, occurring in 10 of the 19 patients, but did not appear to be clinically relevant. Cognitive impairment developed in five of the 15 patients where follow-up was possible. CONCLUSIONS: Mania occurring in advanced HIV disease appears to be more common than expected from epidemiological data regarding bipolar affective disorder. Differentiating secondary from primary mania has implications for the management and prognosis of mania.

Assessment of long-term outcomes of hepatitis C virus infection in a cohort of patients with acute hepatitis in 1971-1975: results of a pilot study.

BACKGROUND: To examine the long-term effects of hepatitis C virus (HCV) infection in a cohort of patients admitted to Fairfield Hospital with hepatitis from 1971 to 1975. The availability of stored sera from this time enabled testing to identify those who were anti-HCV positive on admission. METHODS: Sixteen per cent (n = 230) of the cohort tested positive for HCV antibody (anti-HCV). The 'unexposed' group was selected from those who were anti-HCV negative. Systematic approaches were used to locate the cohort and health outcomes assessed by a study specific questionnaire and clinical review with repeat serology and liver function tests. RESULTS: Complete follow up has been achieved on a subset of 35 HCV-seropositive and 70 seronegative individuals. The seropositive group was significantly more likely to have given a history of injecting drug use, the presumed route of infection. The seropositive group was also more likely to have elevated serum alanine aminotransferase levels, but only two (6%) were known to have progressed to cirrhosis. DISCUSSION: The anti-HCV-positive individuals followed up to date are at increased risk of liver-related pathology, but few had progressed to cirrhotic liver disease. This differs from findings of transfusion-related studies and suggests, within the limitations of the study, that the natural history of community acquired HCV may be more benign.

Percutaneous endoscopic gastrostomy feeding in AIDS.

Reduced energy intake is the most important reason for weight loss in advanced human immunodeficiency virus (HIV) infection. From January 1989 to August 1995 enteral feeding via a percutaneous endoscopic gastrostomy tube (PEG) was offered to all human immunodeficiency virus(HIV)/AIDS patients attending Fairfield Hospital, Melbourne who were unable to maintain 85% ideal body weight. A total of 71 patients received enteral feeding (1000-2000 kcal/day) for a median period of 161 days (range 4-644 days). Fifty-one (72%) patients gained 5.8 +/- 4.4kg (range 0.4-19.2 kg). Nine gained 10 kg or more. The median time to maximum weight was 74 days after PEG insertion. Those who gained weight had a longer median survival, but this difference was not statistically significant (210 vs 109 days, P = 0.07). The only predictor of weight gain was a CD4 count greater than 100/microL. Patients who gained weight reported improved quality of life and increased independence. However, early complications, especially wound infection, were common. Although these data have been gathered retrospectively, our experience suggests that enteral feeding can maintain or improve nutritional status and may improve quality of life in advanced HIV infection.

Trends in incidence of AIDS illnesses in Australia from 1983 to 1994: the Australian AIDS cohort.

To assess time trends in incidence of AIDS illnesses in Australia, a retrospective cohort of people diagnosed with AIDS from January 1, 1983 to December 31, 1994 in three HIV medicine units in Sydney, Melbourne, and Perth was established. Data on initial and subsequent AIDS illnesses were available for 2580 AIDS cases, or 45% of Australian AIDS notifications over the study period. Males represented 97.2% of the cohort, and HIV exposure category was homosexual contact for 89.9%. Subcohorts were formed by interval of AIDS diagnosis: 1983 through 1987, 1988 through 1990, and 1991 through 1994, with estimation of cumulative risk for each AIDS illness by the Kaplan-Meier method. The cumulative risk declined for Pneumocystis carinii pneumonia (PCP) (p < 0.0001) and for Kaposi's sarcoma (KS) (p < 0.0001); PCP cumulative risk estimates 2 years following AIDS diagnosis were 70% for people diagnosed with AIDS in 1983 through 1987 and 48% in 1991 through 1994, and KS cumulative risk estimates 2 years following AIDS diagnosis were 44% in 1983 through 1987 and 32% in 1991 through 1994. In contrast, cumulative risk increased from 34% to 40% for cytomegalovirus (CMV) disease (p = 0.005), from 47% to 50% for Mycobacterium avium complex (MAC) (p < 0.0001), and from 26% to 33% for esophageal candidiasis (p < 0.0001). Corresponding to this changing spectrum of AIDS illness has been an increase in severity of immunodeficiency at AIDS, with median CD4 cell count declining from 54 cells/mm3 in 1983 through 1987 to 34/mm3 in 1991 through 1994 (p = 0.002).

Prognosis of Kaposi's sarcoma as an initial and later AIDS associated illness.

BACKGROUND: The natural history of Kaposi's sarcoma (KS) as a primary presentation of AIDS has been well defined, but little is known about the prognosis of KS following a different AIDS defining illness (ADI). PATIENTS AND METHODS: Retrospective review of 852 consecutive individuals diagnosed with AIDS at Fairfield Hospital between 1984 and 1994. Demographic data, year of diagnosis, CD4 cell counts, treatment for KS and PCP prophylaxis were included in the analysis. Survival following a diagnosis of KS was evaluated, adjusting for the effects of year of diagnosis, primary or secondary KS and degree of immunodeficiency. RESULTS: The overall cumulative incidence of KS by three years post ADI was 34%. Median survival for KS as an ADI (n = 130) was 20 months versus 9 months for KS subsequent to another ADI (n = 75, P < 0.001). Those with KS as an ADI had a higher CD4 count (median 90 vs. 11, P < 0.001), lower incidence of visceral disease (5 of 130 vs. 11 of 75, P = 0.032) and fewer associated AIDS related illnesses (1 vs. 2, P < 0.001). Poorer survival following diagnosis of KS was associated with a lower CD4 count at diagnosis of KS (P = 0.002), extensive cutaneous or visceral KS at diagnosis (P = 0.009 and P < 0.001 respectively) and with the number of associated AIDS related illnesses (P < 0.001). A multivariate analysis suggested that, after adjusting for these factors, there was no difference in survival between primary and secondary KS. CONCLUSION: We found no difference in survival between primary and secondary KS after adjusting for potential confounding factors. We cannot exclude, however, that the greater incidence of visceral disease identified in secondary KS reflects an inherently more aggressive biology.

HIV risk behaviour and HIV testing of psychiatric patients in Melbourne.

OBJECTIVES: Patients with chronic mental illnesses constitute an important risk group for HIV infection overseas. This study aimed to determine the prevalence of risk behaviours associated with HIV transmission and factors associated with HIV testing in psychiatric patients in Melbourne. METHODS: Inpatients and outpatients completed an interviewer-administered questionnaire which covered demographics, psychiatric diagnosis, risk behaviour, and HIV education and testing. RESULTS: Of 145 participants, 60% were male and 55.2% had schizophrenia. Injecting drug use (IDU) was reported by 15.9%, a figure approximately 10 times that found in other population surveys. Most patients reported sex in the last decade and over 20% had multiple sexual partners in the last year. Of males, 12.6% reported sex with another male (9.2% anal sex); 19.0% of females reported sex with a bisexual male. Nearly half of the males reported sex with a prostitute, 2.5 times that in a population sample. Only 15.9% reported ever having someone talk to them specifically about HIV and its transmission, although one-third had been tested for HIV. In multivariate analysis, male-male sex, paying for sex, and IDU were associated with HIV testing, but those whose primary language was not English were less likely to be tested. Those who had received HIV education were more likely to have used a condom last time they had sex (OR 4.52, 95%CI 1.49-14.0). CONCLUSIONS: This study provides evidence that those with serious mental illness in Victoria have higher rates of participation in risk behaviour for HIV infection than those in the general community. Attention to HIV education and prevention in this group has been inappropriately scant; strategies to encourage safer behaviour are urgently needed.

Declining incidence and later occurrence of Kaposi's sarcoma among persons with AIDS in Australia: the Australian AIDS cohort.

OBJECTIVE: To explore trends in cumulative incidence of Kaposi's sarcoma (KS) and the level of immunodeficiency at KS diagnosis among people with AIDS in Australia. SETTING: Three hospital-based HIV units. STUDY POPULATION: Retrospective cohort of 2580 people diagnosed with AIDS over the period 1983-1994, representing 45% of cases of AIDS in Australia over this period. METHODS: Data including date and CD4 T-lymphocyte count of KS diagnosis was abstracted from medical records. KS occurring as both an initial and subsequent AIDS illness was included. Three subcohorts were defined based on interval of AIDS diagnosis: 1983-1987, 1988-1990, 1991-1994. Cumulative risk estimates for KS development were calculated by the Kaplan-Meier method. RESULTS: KS was diagnosed in 716 people (27.8%), and in 451 (63%) of these as the initial AIDS illness. There was a decline over time in cumulative incidence of KS (P < 0.0005); the cumulative risk of KS at 1 year after AIDS diagnosis declined from 35% for those diagnosed with AIDS during 1983-1987 to 25% for 1991-1994. This decline was not due to a decline in homosexual HIV exposure category, and was independent of CD4 T-lymphocyte count at AIDS. In multivariate analysis independent risk factors for KS development were year of AIDS diagnosis (P = 0.003), male homosexuality (P = 0.003), and CD4 T-lymphocyte count at AIDS greater than 150 x 10(6)/l (P = 0.02). A decline in median CD4 T-lymphocyte count at KS diagnosis was seen, from 67 x 10(6)/l in 1984-1987 to 20 x 10(6)/l for 1991-1994 (P < 0.0005). CONCLUSION: The decline in incidence and later occurrence of KS suggest several hypotheses, including declining prevalence or reduced virulence of a KS cofactor.

Managing HIV. Part 6: People living with HIV. 6.2 Women with HIV.

Gay men with HIV often belong to strong mutually supportive groups, but many women with HIV experience the disease in relative isolation. Informed primary care doctors can make a valuable difference to their management.

Managing HIV. Recommendations for antimicrobial prophylaxis in HIV.

Much of the improvement n quality and length of life achieved by HIV medical science is due to primary and secondary prophylaxis for opportunistic infection.

HIV in the mentally ill.

OBJECTIVE: To review the published literature in relation to prevalence of HIV infection and risk behaviours for HIV among the mentally ill to assist in the development of appropriate strategies for public health policy, surveillance and clinical management of HIV and HIV risk in these groups. METHOD: A search of published literature was carried out using 'Medline', in association with following up appropriate papers cited in the references of journals identified. RESULTS: The North American literature shows an increased risk of HIV infection in psychiatric patients receiving treatment in both inpatient or community settings. HIV infection is associated with a number of risk behaviours, particularly male homosexual sex and injecting drug use, and being the sexual partner of a person with a history of these. Impulsivity, high levels of sexual activity during acute exacerbations of psychiatric illness, poor skills at negotiating safe sex, homelessness and drug abuse are all risk behaviours common among those affected by some mental illnesses. The mentally ill also have a comparatively poorer knowledge of HIV/AIDS. There is a dearth of published Australian data addressing the question of HIV seroprevalence or risk in the mentally ill. Although there has been development and implementation of HIV risk-reduction programs overseas, the development and evaluation of any programs in Australia has not been published. CONCLUSIONS: Arguably, Australia has developed a comprehensive program of national surveillance for HIV infection and has been relatively successful in its response to the HIV epidemic, with the high rates of infection in the early to mid-1980s substantially reduced to around 600 new diagnoses per year. However, while risk behaviours which exposed those infected with the virus are recorded, underlying conditions which predispose them to these behaviours are not. Nevertheless, there is HIV infection amongst mentally ill and intellectually disabled people in Australia. Examination of the North American experience reveals opportunities to prevent a high rate of HIV infection in those with mental illness in Australia. Such a program would require adequate risk behaviour assessment, appropriate diagnostic testing and management, and development of specific educational interventions which are properly evaluated to ensure their effectiveness.