THE NATIONAL CENTRE IN HIV EPIDEMIOLOGY AND CLINICAL RESEARCH FOREWORD 2 INTRODUCTION 3 SURVEILLANCE 4 NATURAL HISTORY 8 TRANSMISSION 10

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2 CONTENTS THE NATIONAL CENTRE IN HIV EPIDEMIOLOGY AND CLINICAL RESEARCH FOREWORD 2 INTRODUCTION 3 SURVEILLANCE 4 NATURAL HISTORY 8 TRANSMISSION 10 HEALTH SERVICES 12 CLINICAL TRIALS 14 STAFF 24 ADVISORY COMMITTEES 26 COLLABORATING ORGANISATIONS 32 LECTURES AND TEACHING 36 HIGHER DEGREE AWARDS AND ENROLMENTS 38 SHORT COURSE 38 FUNDING 40 PRESENTATIONS 41 PUBLICATIONS 51 The National Centre in HIV Epidemiology and Clinical Research is funded by the Commonwealth Department of Health and Aged Care through the Australian National Council on AIDS and Related Diseases (ANCARD), and is affiliated with the Faculty of Medicine, The University of New South Wales. ISSN no THE NATIONAL CENTRE IN HIV EPIDEMIOLOGY AND CLINICAL RESEARCH ADDRESS Level 2, 376 Victoria Street, Sydney NSW 2010 Australia TELEPHONE +61(02) FACSIMILE +61(02) WEBSITE ADDRESS recept@nchecr.unsw.edu.au GRAPHIC DESIGN VERMILION DESIGN PRINTING Publishing and Printing Services, UNSW Cover image reproduced with permission from Boehringer Ingelheim 1

3 FOREWORD The National Centre in HIV Epidemiology and Clinical Research continues to maintain and enhance its position as an international leader in the area of HIV/AIDS. While the treatment for those affected by HIV continues to improve with combination antiretroviral drugs, the National Centre faces new challenges which have been met with the usual determination and attention to detail. During 1998, this report indicates these challenges are several fold and include the need for additional studies related to the complications of therapy, the evident need for additional studies of the hepatitis C epidemic etc. The fine quality of the studies performed at the National Centre are supported by the fact that the National Centre maintains and enhances its position of eminence as an international as well as national Centre of Excellence in its field of study. In keeping with the needs of responding to the fast paced research environment, several changes in oversight of the National Centre have been suggested and endorsed. A new Scientific Advisory Committee will concentrate on oversight of the scientific research undertaken by the National Centre. I commend the contents of this annual report to all and look forward to the continuation of the excellent work encompassed in the activities of the National Centre at present as it moves forward into the future period. S. Bruce Dowton S. BRUCE DOWTON S. Bruce Dowton Chair, Management Committee National Centre in HIV Epidemiology and Clinical Research Dean, Faculty of Medicine The University of New South Wales 2

4 INTRODUCTION In the area of HIV/AIDS and related diseases research, 1998 once again presented the National Centre with numerous challenges. The use of combination antiretroviral therapy for the treatment of HIV related disease seems to be effective as our surveillance research indicates a steady decline in the number of AIDS diagnoses in Australia since This is matched by a decline in the annual number of HIV diagnoses. These encouraging figures can be found in the National Centre s quarterly surveillance reports and the highly successful Annual HIV Surveillance Report 1998, which became available for the first time on the world wide web. However, along with the improvements and greater choice in antiretroviral treatment for HIV/AIDS are the complications. We are increasingly finding that this therapy does not work for everyone or is producing significant long-term adverse effects. During 1998, the National Centre continued to investigate some of the more serious side effects of these drugs in addition to conducting clinical trials to determine effective therapeutic strategies and solutions for people living with HIV/AIDS. The gap in HIV/AIDS treatment between the developing world and the developed world seems to be widening, and this was certainly brought home to us at the 12th International AIDS Conference in Geneva in June. With the soaring rates of HIV infection in Africa and Asia and the affected countries immense differences in standards of care, effective clinical trials in these regions are critically important. The National Centre continued to successfully collaborate in international studies, such as HIVNAT, based in Bangkok Thailand, a program with the Thai Red Cross Society s Program on AIDS and the Dutch National AIDS Therapy Evaluation Centre, to investigate appropriate therapeutic treatments in local settings. During 1998, the National Centre continued to investigate the hepatitis C epidemic, which is now of increasing concern for those planning a public health response. Through the Australian National Council on AIDS and Related Diseases hepatitis C sub-committee, the National Centre coordinated the hepatitis C projections working group to provide estimates of HCV incidence and prevalence in Australia. This report was published in August and gives an alarming indication of the extent of hepatitis C within Australia. Although resources are sometimes limited, the staff at the National Centre should be credited for their outstanding efforts and commitment to improving the understanding of HIV/AIDS and related diseases. The number of scientific publications that have been produced as a result of their research is an indication of the National Centre s achievements in this area. Yet most of this would not be possible without the continued tremendous support from the different sectors of the AIDS community and interested organisations and individuals. DAVID A.COOPER I would also like to thank the National Centre s Management Committee members for their invaluable advice and encouragement over the years. From 1999, the National Centre will be advised by a new Scientific Advisory Committee, who will report to ANCARD through its Research Advisory Committee and will concentrate on reviewing and advising on the scientific research undertaken by the National Centre. David A. A. Cooper Professor of of Medicine and and Director National Centre in in HIV HIV Epidemiology and and Clinical Research The The University of of New New South South Wales Wales 3

5 SURVEILLANCE JOHN KALDOR HIV/AIDS AND RELATED DISEASES IN AUSTRALIA - ANNUAL SURVEILLANCE REPORT 1998 The National Centre edited the second comprehensive annual summary of current knowledge on the pattern of HIV infection, AIDS and related diseases in Australia, HIV/AIDS and related diseases in Australia Annual Surveillance Report This reference document, prepared with the collaboration of many health related services in Australia, is aimed at supporting the development and implementation of policy and programs aimed at the control of these infectious diseases. For the first time, the report became accessible on the World Wide Web ( The Annual Surveillance Report 1998 presented estimates of 11,150 people living with HIV infection in Australia by the end of 1997, including 2,190 people living with AIDS. A steady decline in AIDS incidence was observed from 1994 to 1996, attributable to the fall in HIV transmission in the mid-1980s. A much more marked decline in AIDS incidence was observed in 1997, probably due to the introduction of more effective antiretroviral therapy. Although ongoing transmission of HIV continues to be documented in Australia, primarily among men who have sex with men, there was no evidence for increased rates of HIV transmission. Among injecting drug users, high rates of hepatitis C infection continued whereas the prevalence of HIV in this population remained below 2%. Professor John Kaldor Deputy Director Information on the pattern of diagnosis of HIV infection and AIDS in Indigenous people was also included in the Annual Surveillance Report Over the period , there appears to be no evidence of an increase in HIV transmission. Although male homosexual contact was the primary route of HIV transmission in both Indigenous and non-indigenous cases, a higher proportion of cases in Indigenous people was among females, and attributed to heterosexual contact. A substantially higher rate of diagnosis of specific sexually transmissible infections among Indigenous people compared with non-indigenous people was reported from three State/Territory health jurisdictions with information on Indigenous status available in more than 50% of diagnoses. Seventy five percent of people diagnosed with AIDS in Australia in were born in Australia; AIDS incidence among people born overseas, following adjustment for age, was substantially lower than that among the Australian born. The National Centre continued to publish quarterly the Australian HIV Surveillance Report. These reports provide regular updates on the number of diagnoses of HIV infection and AIDS in Australia as well as HIV incidence and prevalence available through a network of sexual health clinics. In addition, updates of the number of diagnoses of HIV infection and AIDS in the WHO Western Pacific Region were included. Special interest features were also published in the reports: HIV prevalence and incidence among injecting drug users attending needle and syringe exchanges in Australia in ; trends in the HIV/AIDS epidemics in Asia and the Pacific; a report from the 12th World AIDS Conference; and uptake of antiretroviral treatments in Australia in Status: Ongoing. 4

6 IMPROVEMENTS IN ROUTINE CASE REPORTING OF HIV AND AIDS Routine case reporting of HIV and AIDS is continually being refined and upgraded in order to rectify any weaknesses in the data collected. A project designed to monitor the completeness of notification of AIDS diagnoses and death following AIDS was established in 1998, in collaboration with the Australian Institute of Health and Welfare (AIHW). Deaths registered with the National Death Index for which the cause of death was attributable to AIDS were matched with National AIDS Registry deaths. Deaths attributable to AIDS that could not be matched with AIDS cases notified as having died will be followed up through State/Territory health authorities to establish if the person had, in fact, died following AIDS. Status: Ongoing. MONITORING HIV INFECTION AMONG PRISON ENTRANTS IN AUSTRALIA The National Centre, in collaboration with State/Territory Departments of Corrections, has monitored the extent and outcome of testing for HIV antibody at prison entry in Australia from HIV antibody testing was carried out for 72% of prison entrants in The extent of HIV antibody testing at reception varied over time and by jurisdiction. HIV prevalence at reception into Australian prisons remained at less than 0.5% throughout the 7 year interval. gay communities of Melbourne, Brisbane, Perth and Adelaide in addition to Sydney, where monitoring has taken place since Although some locally specific issues are addressed in each city, the project primarily is a cross-sectional survey of risk behaviour and contexts among gay men in these cities. Data collected includes: sexual behaviour with regular and casual partners, HIV testing patterns and results, use of antiviral treatments, association with the gay community. During 1998, over 7,500 gay men were surveyed across these cities, with 3,000 respondents from Sydney. Results are to be published in reports for each city. Status: Ongoing. SYDNEY WOMEN AND SEXUAL HEALTH (SWASH) In 1998, a cross-sectional survey was carried out in collaboration with NCHSR of risk behaviour and their contexts among women in contact with men in the Sydney gay community. This survey was first carried out in 1996 primarily to find out if further research or prevention campaigns were necessary for these women. The data collected included: sexual behaviour with regular and casual partners, HIV testing patterns and results, recreational drug use, association with the gay community. The preliminary findings were that the majority of respondents had friends in the gay community; two thirds of the women interviewed regarding themselves as lesbian; and over one quarter had sex with a man they knew to be gay or bisexual. Status: Ongoing. Status: Completed; NCHSR Monograph. AUSTRALIAN GAY COMMUNITY PERIODIC SURVEYS Through a continuing collaboration between the National Centre and the National Centre in HIV Social Research (NCHSR), The Australian Federation of AIDS Organisations (AFAO) and the National Association of People Living With HIV/AIDS (NAPWA), this project is designed to regularly monitor changes in sexual behaviour among gay men, particularly those behaviours associated with HIV transmission. In 1998, the surveys were conducted for the first time in the HIV AND HEPATITIS C VIRUS ANTIBODY AND INJECTING AND SEXUAL BEHAVIOUR AMONG INJECTING DRUG USERS ATTENDING NEEDLE AND SYRINGE PROGRAMS The fourth annual national survey of HIV and hepatitis C (HCV) antibody prevalence and injecting and sexual behaviour among injecting drug users attending needle and syringe programs (NSEP) was carried out in October All clients attending selected needle and syringe exchange programs during the designated survey week were asked to 5

7 completed a brief, self administered questionnaire and provide a finger prick blood sample for HIV and HCV antibody testing. Thirty one needle and syringe programs participated in the 1998 survey, a considerable increase on the 20 programs in the initial year. Completed questionnaires were received from 2,670 participants. Once again, four NSEP in New Zealand participated in the survey and this year the study included four pharmacies in South Australia to assess the feasibility of using pharmacy sites for future investigations. Status: The survey will be repeated annually each October. For the 1998 survey, data analysis will be carried out in May/June ACCIDENTAL EXPOSURE TO BLOOD BORNE VIRUSES AMONG HEALTH CARE WORKERS Since July 1995, a nationwide network of hospitals has provided information on occupational exposures to blood and body fluids. In 1997, the number of hospitals participating increased to 56 sites from the initial 13 sites. Data for 1998 will be collected in April 1999 to allow for three months follow-up after exposures. Results have shown that prevalence of HIV, hepatitis B (HBV) and hepatitis C (HCV) infection among sources tested following exposures to health care workers was 3.2%, 10.1% and 32.9% respectively. A small proportion of health care workers (1.0%) exposed to a source with HIV infection were prescribed antiretroviral prophylaxis for HIV infection. No seroconversion to HIV, HBV nor HCV infection was reported but information on testing at three months post exposure was only available for one third of exposures.during 1998, to improve data entry and report writing for participating sites, the National Centre, in collaboration with Becton Dickinson Pty Limited, carried out extensive upgrading of the database used at the participating sites to collect information for this project. Status: Ongoing. HEPATITIS C VIRUS PROJECTIONS WORKING GROUP The surveillance and monitoring of hepatitis C presents researchers with a number of methodological challenges, as newly acquired infection is difficult to detect being generally asymptomatic. Other problems are associated with the accessibility of population groups such as drug users, who are at high risk of transmission, the long-term course of the disease and the ongoing coordination of diagnostic methodology. The Hepatitis C Virus Projections Working Group was set up in late 1997 under the hepatitis C subcommittee of Australian National Council on AIDS and Related Diseases (ANCARD) primarily to provide consensus estimates of HCV incidence and prevalence in Australia. The Working Group also sought to obtain projections of the long-term consequences of HCV infection and to identify gaps in HCV research. Chaired by Dr Alex Wodak, and supported by the National Centre, the Working Group comprised clinicians, epidemiologists, statisticians and mathematical modellers, health economists, and representatives of the State/Territory Health Departments, the Commonwealth and the Australian Hepatitis Council. The Working Group met regularly to extensively review the epidemiology of hepatitis C. Direct estimates of hepatitis C prevalence were based on available serosurveys. Estimates and projections were also obtained using mathematical models based on an assumed pattern of injecting drug use in Australia. The results were published in the group s final report Estimates and Projections of the Hepatitis C Virus Epidemic in Australia in August Among the more significant findings were that by the end of 1997 there were 196,000 people estimated to be living in Australia with HCV, with 11,000 new HCV infections in that year. It was further estimated that there were 8,500 people living with liver cirrhosis, and 80 incident cases of hepatocellular carcinoma as a result of HCV in 1997, with both conditions predicted to more than double by Status: Completed; journal publication (Journal of Hepatitis and Gastroenterology); report published August

8 NATIONAL HEPATITIS C SURVEILLANCE STRATEGY Under the auspices of the Communicable Diseases Network Australia New Zealand (CDNANZ), a committee was established in 1998 to develop and implement a national strategy to improve the surveillance of HCV in Australia. Committee members include representatives with experience in hepatitis C surveillance from each State and Territory, as well as representatives from the ANCARD HCV Working Party, the Public Health Laboratory Network and the National Centre for Disease Control. relating to the collection of Indigenous mortality statistics in Australia and the possible reasons for inaccuracies in the data and to make recommendations for the improvement of the current system of data collection. During 1998, negotiations with Aboriginal Medical Services expressing an interest in the study took place. This study, carried out by a student placement from the National Centre for Epidemiology and Population Health (NCEPH), will continue during Status: Results are expected by December During 1998, the committee developed a draft strategy and presented it to the CDNANZ for endorsement. This strategy incorporated routine case reporting of HCV incidence and monitoring sentinel populations for HCV prevalence as well as surveillance for long-term outcomes of HCV infection. Status: Ongoing. INCIDENCE OF HEPATITIS C AMONG A COHORT OF SYDNEY INJECTING DRUG USERS Through collaboration with the Kirketon Road Centre (KRC), the National Centre has been involved in the ongoing monitoring of hepatitis C transmission among injecting drug users, the population group at highest risk of this blood borne virus. The incidence over the period has been approximately 20/100 person years. Factors associated with seroconversion included age less than 20 years and history of incarceration. Transmission over the period is currently being analysed. Status: Journal publication (British Medical Journal) of incidence over period ; analysis of data underway. UNDER-REPORTING OF INDIGENOUS MORTALITY STATISTICS Accurate data on Indigenous mortality are important for the appropriate allocation of health resources, addressing underlying causes of death and for evaluating interventions designed to alleviate those causes. The aim of this project is to explore some of the issues 7

9 NATURAL HISTORY HOST GENETIC FACTORS ASSOCIATED WITH LONG-TERM ASYMPTOMATIC HIV-1 INFECTION. An important and evolving area of HIV research in the past few years has been the search for host genetic characteristics that influence disease progression. A particularly productive area has been the investigation of the cell surface receptors that influence the ability of HIV to infect cells. Cellular entry of HIV-1 has been shown to require binding to both the CD4 cell protein and to one of two co-receptors: the alpha chemokine receptor or the beta chemokine receptor CCR5. The National Centre, in collaboration with Westmead Hospital, is currently examining variation among individuals that occur within the chemokine co-receptor genes, CCR5 and CCR2b. In the Australian long-term nonprogressor (LTNP) cohort a higher frequency of mutation for CCR5-32 and CCR2b-64I were observed in LTNPs compared to rapid progressors. Preliminary results suggest that these mutations together with certain HLA class I alleles may be more abundant in LTNPs and contribute to delayed disease progression. Status: Ongoing. CHEMOKINE CO-RECEPTORS: ASSOCIATIONS WITH SPECIFIC OPPORTUNISTIC INFECTIONS. As well as influencing disease progress in general, genetic markers may play a role in susceptibility to specific opportunistic infections. The association between CCR5 and CCR2b genotypes and clinical signs of first and subsequent AIDS defining illnesses was investigated in a cohort of homosexual men. pattern continued for these opportunistic infections occurring subsequent to the first ADI. Individuals heterozygous for CCR5-32 had fewer cases of PCP, toxoplasmosis, MAC, and cryptosporidiosis as subsequent ADIs than expected, based on rates measured in the same hospital during the same period. Such associations were not found for the CCR2b-64I mutation. These findings suggest that expression of the CCR5-32 mutation but not the CCR2b-64I mutation appears to protect against the development of certain ADIs, particularly those caused by certain intracellular pathogens. Status: Completed. HIV-1 SPECIES DIVERSITY IN LTNPS The viral species present in individuals infected with HIV-1 can vary enormously. Previous studies have suggested that viral diversity may play a role in HIV-1 pathogenesis. Viral diversity was examined in an Australian cohort of longterm nonprogressors (LTNPs), with a particular focus on diversity in the nef/ltr region of the HIV-1 genome. Increased genetic diversity in the nef/ltr region of the HIV-1 genome was found to be correlated with decreased levels of CD4+ T-cells, increased levels of HIV-1 RNA, serum ß2-microglobulin and a lower frequency of CCR2b-64I heterozygosity. Although increased viral diversity was associated with an increased risk of disease progression, the strongest predictors of progression were lower CD4+T-cell count and higher plasma levels of HIV-1 RNA in these individuals. Status: Ongoing, journal publication (AIDS Res Hum Retroviruses). The incidence of Pneumocystis carinii pneumonia (PCP), toxoplasmosis, Mycobacterium avium complex (MAC) infection and cryptosporidiosis reported as a first ADI was substantially fewer in people heterozygous for the CCR5-32 mutation than for those without the mutation, despite similar age, CD4+ T-cell count at AIDS diagnosis, year of AIDS diagnosis and receipt of antiretroviral treatment. The AIDS DIAGNOSES AT HIGHER CD4 COUNTS IN AUSTRALIA FOLLOWING THE INTRODUCTION OF HIGHLY ACTIVE ANTIRETROVIRAL TREATMENT Although the incidence of AIDS has declined rapidly in Australia following the introduction of highly active antiretroviral therapy (HAART), there have been some reports of an increase in AIDS diagnoses made at relatively high CD4 counts. Data on CD4 count at AIDS diagnosis for 8

10 cases reported to the National AIDS Registry were analysed, by year of diagnosis and for each illness separately. linkage with the National Cancer Statistics Clearing House at AIHW. Status: Linkage to occur in June/July There was an increase in CD4 count at AIDS diagnosis in 1996 and 1997, though this increase was only apparent for AIDS defining illnesses other than PCP, and was limited to people who had been diagnosed with HIV more than three months prior to AIDS. In cases of AIDS other than PCP, and diagnosed with HIV more than three months prior to AIDS, the median CD4 count increased from 50 cells/µl in 1996 and 134 cells/µl in Status: Completed; publication submitted (AIDS). TRENDS IN AIDS DEFINING ILLNESSES IN THE ERA OF IMPROVED ANTIRETROVIRAL THERAPIES To investigate the effect of improvements in antiretroviral therapy, recent trends in the incidence and spectrum of AIDS defining illnesses (ADI) in Australia were examined on the National AIDS registry. People who were diagnosed with HIV at the time of AIDS diagnosis were compared with other people with AIDS. The results showed that AIDS incidence in Australia has dramatically declined in recent years, however people with unknown HIV infection are constituting an increasing proportion of AIDS cases and have a different spectrum of ADIs. Status: Completed. THE RISK OF CANCER IN PEOPLE WITH HIV/AIDS In 1997, a study was completed in NSW that showed, via linkage of the NSW cancer and state AIDS registers, that the rates of Hodgkin s disease and other rare forms of cancer are increased in people with HIV/AIDS. These data suggested that a wider range of cancers than previously described might occur at increased rates in people with HIV and AIDS. In order to further investigate these patterns, the National Centre is extending these observations through a national study involving AIDS DEMENTIA COMPLEX: A CASE-CONTROL ANALYSIS To assess the risk factors for the development of ADC and survival following ADC diagnosis, a case-control analysis was undertaken, with 110 cases and 110 controls from the St Vincent s Hospital HIV Unit. This study formed part of a broader, ongoing study of ADC at St Vincent s Hospital. The main findings from this study were that older age; other neurological disorders such as myelopathy; psychiatric disorders such as hypomania and depression; and absence of Kaposi's sarcoma were associated with ADC. In addition, this study suggests that survival following ADC is strongly correlated with stage of ADC at diagnosis. Status: Data collection and analysis completed; MPH treatise submitted; paper in preparation. RECENT EPIDEMIOLOGY OF AIDS DEMENTIA COMPLEX A study was conducted to assess changes in the incidence of ADC since the introduction of improved antiretroviral therapy. AIDS illness notifications to the Australian National AIDS Registry (NAR) over the period were examined to detect changes to the incidence of AIDS dementia complex (ADC) relative to other AIDS defining illnesses. Although there has been a decline in incidence of ADC in recent years, this decline appears to be relatively less than for other AIDS illnesses. Thus, improved antiretroviral therapy may be less protective against ADC than for many other AIDS illnesses. Status: Data collection and analysis completed; journal publication (AIDS). 9

11 TRANSMISSION SYDNEY MEN AND SEXUAL HEALTH (SMASH) This long-term cohort study of HIV-related risk behaviour and its social context among a cohort of gay men in Sydney continues for the sixth year. The project has closely monitored trends in risk practices and responses to HIV, while attempting to measure the incidence of HIV infection and identify its risk factors. Data collected include self-reported sexual behaviour with regular and casual partners; HIV testing patterns and results; use of antiviral treatments; recreational drug use; and association with the gay community. This study has consistently produced crucial information about HIV infection and related factors in homosexually active men. Status: Ongoing. PERCEPTIONS OF RISK AMONG MEN WHO USE SEX ON PREMISES VENUES A study was undertaken in 1998 in collaboration with the NCHSR and AFAO to examine the reasons why men who are at risk for HIV seroconversion have unprotected intercourse, as well as determining their perceptions of relative risk. A study of perceptions of risk behaviour and contexts among gay men using sex on premises venues in Sydney was undertaken. During 1998, twenty in-depth interviews were completed. This qualitative data complemented quantitative data collected through the SMASH study to explore sexual networks and understandings of the meanings of sexual behaviour and subcultures within the contexts of sex on premises venues. The results are to be published in a report during Status: Completed. qualitative study of infant feeding attitudes and practices among 200 antenatal and postnatal women in Chiang Rai Province in northern Thailand was carried out in 1998 by an MPH student supervised through the National Centre. The study population consisted of antenatal HIV-infected women, postnatal HIV-infected women, and a control group of antenatal women of unknown HIV status. The survey showed that knowledge about HIV infection was good in general and specific knowledge levels related to mother to child transmission were also high. Breast feeding was considered to be much more advantageous than formula feeding. Despite this, the vast majority of postnatal and antenatal women with HIV infection formula fed, or planned to formula feed, their infants. Status: Data collection completed; MPH treatise submitted; paper in preparation. ANALYSIS OF HIV VOLUNTARY TESTING AND COUNSELLING CENTRES IN CAMBODIA The number of people infected with HIV/AIDS in developing countries such as Cambodia continues to grow rapidly. A study was carried out by an MPH student supervised through the National Centre to determine the HIV prevalence and risk factors for HIV infection among people who attend HIV voluntary testing and counselling centres for HIV in Cambodia. More than 15,000 people were tested for HIV infection at six centres in Cambodia over the period An analysis was conducted of the demographic and behavioural factors associated with HIV incidence and prevalence within this population. ATTITUDE TO INFANT FEEDING AND PRACTICES AMONG WOMEN IN NORTHERN THAILAND Breast feeding in HIV infected women is of concern, particularly in developing countries, as it has been found to increase the risk of the virus being transmitted from mother to child. To assess the impact this has had on the mother s approach to breast feeding, a quantitative and The prevalence of HIV was found to have increased from 14% in 1995 to 17% in 1997 at these centres. The study also showed that provinces in the north-west near the Thailand border, occupations such as sex workers, military, police, farmers, traders and labour workers, illiteracy, and sexual behaviour, in particular the absence of condom use, were 10

12 significantly associated with HIV infection. Status: Data collection and analysis completed; MPH awarded; paper in preparation. KAPOSI S SARCOMA HERPESVIRUS: RISK FACTORS FOR INFECTION AND VERTICAL TRANSMISSION IN JOHANNESBURG, SOUTH AFRICA The human herpes virus 8 (HHV-8) has been found to cause Kaposi s sarcoma but a number of questions remain about the mode of transmission and HHV-8 pathogenesis. The National Centre has commenced a collaborative study in South Africa to determine the seroprevalence of HHV-8 in women with HIV. The study will also investigate whether HHV-88 is vertically transmitted and to find risk factors for HHV-8-8 infection in women with HIV. Study participants are women and children enrolled in the Soweto (Johannesburg) arm of the PETRA randomised controlled trial of mother to child transmission of HIV which has been ongoing for the past two years. A short questionnaire administered to mothers will identify risk factors for HHV-8 infection such as vaginal versus caesarean delivery, breast feeding and receipt of antiretroviral therapy. Serum from approximately 400 mother-infant pairs is to be tested for HHV-8 to estimate the rate of mother to child transmission of HHV-8. Status: Testing to occur mid INVESTIGATION OF HEPATITIS A OUTBREAK IN NORTHERN RIVERS AREA OF NSW A study to investigate an outbreak of hepatitis A that occurred between December 1997 and August 1998 in the area covered by the Northern Rivers Area Health Service commenced in October A student placement from the NCEPH is carrying out this study. Status: Results are expected in early

13 HEALTH SERVICES MONITORING TREATMENT UPTAKE: A PILOT STUDY As HIV treatments continue to improve, the monitoring of uptake and impact of therapy becomes an important focus of HIV surveillance. One method for achieving this is by collecting observational data on patients in the course of routine clinical management. A pilot study, set up under the direction of Clinical Trials and Treatment Advisory Committee (CTTAC), assessed the feasibility of combining data from existing computerised data bases at three sites (two general practices, Prahran Market Clinic, Melbourne and Holdsworth House General Practice, Sydney and one hospital, Royal Perth Hospital, WA). The record systems were aggregated in early 1998, in an entirely anonymous fashion, into a centralised database using electronic transfer of data. COMMUNITY ATTITUDES TO THE NEEDLE AND SYRINGE PROGRAM, DISCARDED SYRINGES AND PUBLIC INJECTION In 1998, NSW Health commissioned the National Centre to carry out an assessment of the community impact of a new health service aimed at injecting drug users that included a needle and syringe program. The National Centre, around the time of the service opening twelve months earlier, had carried out a baseline evaluation. Community attitudes to the needle and syringe program and community perception of public injecting and discarded syringes were compared between the two surveys. A count of syringes discarded on the street was also repeated in Status: Data collection completed; results due to be released early The study showed that combining electronically recorded data from several sites was possible. Data were collected on 1073 patients, of whom 71% were receiving antiretroviral treatment, and 60% were taking at least three antiretroviral drugs in combination. The study also found that more aggressive treatment was related to HIV disease stage and exposure category. An expanded observational database involving more sites and prospective data collection is planned for commencement in the first half of Status: Pilot study complete; report to CTTAC May POSITIVE HEALTH (PH) STUDY In 1998, the National Centre, in collaboration with the NCHSR, NAPWA and AFAO, initiated a longitudinal study among a cohort of HIV positive people in NSW and Victoria to identify social and behavioural factors particularly associated with the new treatments for HIV. The study will examine the socio-behavioural contexts in which HIV treatments, service utilisation and health-related behaviour practices occur among HIV positive individuals. During 1998, over 150 HIV positive people were enrolled in the study, with ongoing enrolment to continue throughout 1999 until a target number of 350 is reached. The specific data to be collected includes: use of HIV treatments; viral load and CD4 testing patterns and results; access to HIV services and support; recreational drug use; and association with other positive people. The first follow-up for the study is planned for late Status: Ongoing. 12

14 NON-OCCUPATIONAL HIV POST EXPOSURE PROPHYLAXIS Post exposure prophylaxis (PEP) has been available for health care workers in Australia for some time, but those exposed to HIV infection in non-occupational settings did not have similar access to therapy until recently. During late 1998, NSW Health became one of the first health authorities in the world to introduce guidelines on the use of antiretroviral therapy in people exposed to HIV, including those exposed in non-occupational settings. The National Centre, in collaboration with NSW Health, has designed an observational study to follow the appropriateness, extent and efficacy of the use of this therapy. The study will monitor the use of non-occupational post exposure prophylaxis through prescribing doctors, who will provide details of the source person and the event leading to HIV exposure. Details of patient compliance and side effects of the therapy will be provided at four weeks post-exposure. At six months, data on whether or not the patient became HIV infected after the exposure will be given. In collaboration with the National Centre in HIV Social Research. The study will also explore the context of the HIV exposure through patient interviews to gain greater insight into the circumstances in which people become exposed to HIV and the reasons for requesting post-exposure prophylaxis. Status: Data collection to begin in January

15 CLINICAL TRIALS INTRODUCTION During 1998, and following approval of the fiveyear plan by the Commonwealth Department of Health through ANCARD, some important administrative changes occurred at the National Centre within the groups responsible for therapeutic research. Primarily, the Community HIV Research Network (CHRN) and the Clinical Trials Unit (CTU) were unified under one administrative unit - the Therapeutic Research Unit. This internal modification serves two critical objectives, firstly preserving the capacity to support community research with dedicated and experienced personnel and resources and secondly, streamlining internal procedures removing duplication of effort particularly at a time when the research programs of the community and hospital networks are essentially similar. The clinical trial program has remained focussed upon studies of combination antiretroviral therapies. Flowing directly from the important Australian clinical observations of a lipodystrophy syndrome associated with the use of HIV protease inhibitors, the NCHECR network developed a national prevalence survey to determine definitions and the true extent of this clinical manifestation. Importantly, the extent to which the phenomena might or might not be reversible upon cessation of HIV protease-inhibitors, at no penalty to control of plasma HIV concentration was examined in the PIILR study. The speed with which this study was implemented and completely recruited is a great credit to the network. Results from this important trial are anticipated during the latter half of The Ozcombo I and II studies were closed to recruitment in December. Both studies proved popular among recruiting investigators and data will be presented during 1999/2000. Having recruited well, the studies represent an ideal platform from which additional research might flow. For example, the participant cohort will be invaluable in determining aspects of treatment-induced toxicities arising from HIV protease inhibitors, nucleoside analogue reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitors. The cohort will also be invaluable in addressing some aspects associated with the development of drug resistance. The CHRN 025 study was also closed to recruitment with final data expected to be available during the latter part of Work on individuals diagnosed with primary HIV infection in a research setting remained an important component of the NCHECR network effort. Clinical studies continue, through a network of experienced investigators closely aligned to laboratories performing sophisticated monitoring. With treatment of primary HIV infection becoming more common as a routine practice driven intervention, the NCHECR network is attempting to develop research proposals that might determine the validity of such an approach. This is particularly relevant given the failure of eradication strategies, the growing realities of treatment related toxicities, the difficulties of compliance with complex treatment regimens and the lack of evidence indicating that routine treatment is justified. RESEARCH SUMMIT Following the five-year review, conducted in 1997, the NCHECR network and its research program were again the subject of inquiry during the conduct of a CTTAC convened Research Summit held in July. While the terms of reference for the summit were broad and include all National Centre research, it was clear that most focus was brought to bear upon the therapeutic research program of the NCHECR network. The summit did single out areas where the network might attempt to increase its research activity, but more importantly identified that methodologically there were perhaps opportunities to adopt new approaches (eg observational databases). In this regard, the NCHECR network was able to contribute to a pilot observational database (see epidemiology unit) that has since been expanded. The use of observational data base research should compliment continued examination of treatment and treatment strategies in randomised controlled trials. It is in the area of 14

16 treatment strategy that randomised clinical trials are expected to play a continued role in research. The HIV Connect INITIO study, the follow-up to the Ozcombo I and II studies, are important examples of this approach. During 1998, work also continued to examine interleukin-2 therapy as a potential treatment for HIV disease. THE HIV-NETHERLANDS AUSTRALIA THAILAND RESEARCH COLLABORATION (HIVNAT) More than 90% of worldwide HIV infections occur in developing countries and from a regional perspective this has important implications. It is estimated that some 1 million Thai people are infected with HIV and each year approximately 5-6% of these individuals (50,000) will develop AIDS while 35,000 will die. Until recently very little research had been performed to evaluate HIV therapeutics in the context of the Thai health-care setting and patient groups. submitted for publication. HIVNAT has also organised several educational meetings to update regional physicians and other health care and laboratory personnel in Thailand on the care of HIV-infected patients and GCRP. The staff has expanded rapidly from the initial Dutch clinical research physician and a Thai clinical research nurse. At present, HIVNAT employs an Australian clinical research physician (Mark Newell until October 1998, Chris Duncombe since November 1998), two Thai physicians, a medical statistician, additional Thai research nurses, a data manager, a secretary and laboratory personnel. Initially, trials were limited to a single recruiting site based at Chulalongkorn Hospital in Bangkok. More recently, studies have included additional sites in the Bangkok metropolitan area. In the near future this network should expand to include more institutions in both Bangkok and throughout Thailand. Since July 1996, HIVNAT, a collaboration between the National Centre, the Dutch National AIDS Therapy Evaluation Centre (NATEC, University of Amsterdam) and the Program on AIDS of the Thai Red Cross Society, has been running HIV/AIDS clinical studies at study sites in Thailand from a base in Bangkok at the Thai Red Cross Society. HIVNAT endeavours to demonstrate clinically effective and affordable treatments for Thai nationals with HIV infection in accordance with Good Clinical Research Practice (GCRP). HIVNAT also plays a role in the delivery of health care to Thai nationals with HIV infection, in consultation with the pharmaceutical industry, government and non-government sectors. Currently, three follow-up studies are in progress with three new trials close to commencement. HIVNAT has successfully completed four studies, two of these have been subject to audit by pharmaceutical sponsors with very positive outcomes. Completed studies have been presented at several international meetings and two manuscripts have been 15

17 PRIMARY HIV INFECTION CURRENT STUDIES QUEST Description An open label randomised study of induction therapy with 4 antiretroviral drugs followed by maintenance therapy with three drugs then treatment discontinuation in primary HIV infection. Status opened Nov 98 Sites 9 Enrolled/target 12/open Sponsor Glaxo Wellcome Contact Pat Grey, Don Smith CHRN014 Description An open label study to determine the safety and efficacy of combination antiretroviral therapy (AZT + 3TC + IDV) in patients with primary HIV infection. Status opened July1996, initial phase complete, extension phase continuing Sites 8 Enrolled/target 8/8 Sponsor Merck / NCHECR Contact Pat Grey, Don Smith CHRN 015 Description An open label study to determine the antiretroviral activity and safety of nelfinavir + zidovudine + lamivudine in patients with primary HIV infection. Status opened May 1997, ongoing, enrolment closed Dec 98 Sites 8 Enrolled/target 28/24 Sponsor Agouron Contact Pat Grey, Don Smith Description Status Sites Target Sponsor Contact STUDIES IN PREPARATION AIEDRP ACUTE HIV INFECTION AND EARLY DISEASE RESEARCH PROGRAM An open label study of the effects of combination antiretroviral therapy with abacavir, efavirenz, indinavir and lamivudine in acute HIV-1 infection with an emphasis on immunological responses. in preparation for review for review University of Washington / Division of AIDS, NIH USA / NCHECR Don Smith, Mark Newell Description Status Sites Target Sponsor Contact PULSE A randomised trial of combination therapy plus or minus hydroxyurea for primary HIV infection followed by a regimen of treatment interruption based on HIV-RNA load. in preparation for review for review NCHECR Pat Grey, Don Smith 16

18 AVIPOX VACCINATION Description A randomised evaluation of avipox vaccine in patients treated with combination therapy since seroconversion. Status in preparation Sites for review Target 20 Sponsor to be determined Contact Pat Grey, Don Smith ANTIRETROVIRAL THERAPY COMPLETED STUDIES ABACAVIR VIRAL RESISTANCE TESTING STUDY Description A study of virus resistance in patients with advanced HIV infection on abacavir. Status completed 1997 Sites around Australia Enrolled/Target 35/35 Sponsor Glaxo Wellcome / NCHECR Contact Gillian Hales, Kate Clezy BI 1090 Description A randomised, placebo-controlled trial to evaluate the safety and efficacy of nevirapine in the prevention of AIDS when used in combination with 3TC and stable background nucleoside analogue therapy. Status opened March 1996, enrolment closed December 98 Sites 7 Enrolled/Target 14/open Sponsor Boehringer Ingelheim Contact Pat Grey, Don Smith HIVNAT 001 (THAILAND) Description A randomised, double-blind trial of reduced vs standard dose of zidovudine + zalcitabine in Thai HIV-1 infected patients. Status complete, manuscript submitted for publication Sites 1 Enrolled/Target 116/110 Sponsor HIVNAT / Roche Thailand / Thai Ministry of Public Health / NCHECR Contact Chris Duncombe / Sean Emery HIVNAT 002 (THAILAND) Description A trial of ddi / d4t high:low dose combinations in antiretroviral naive Thai adults with CD4+ counts /mm3. Status complete, manuscript in preparation Sites 1 Enrolled/Target 78/75 Sponsor HIVNAT / Bristol-Myers Squibb Thailand / Thai Ministry of Public Health / NCHECR Contact Chris Duncombe, Sean Emery 17

19 HIVNAT 003 (THAILAND) Description A randomised, open-label comparative trial of AZT/3TC vs. AZT/3TC/ddI in antiretroviral naive HIV-1 infected patients. Status enrolment and follow-up complete, manuscript in preparation Sites 2 Enrolled/Target 106/100 Sponsor HIVNAT / Bristol-Myers Squibb Thailand / Glaxo Wellcome Thailand / Thai Ministry of Public Health / NCHECR Contact Chris Duncombe, Sean Emery CURRENT STUDIES OZCOMBO I Description A randomised comparison of three triple combinations of antiretroviral agents including indinavir in patients who are antiretroviral naive. Status study completed December 1998, manuscript in preparation Sites 27 sites in Australia and New Zealand Enrolled/target 109/120 Sponsor Glaxo Wellcome / Bristol-Myers Squibb / Merck Sharpe and Dohme / NCHECR Contact Jeff Hudson, Sean Emery OZCOMBO II Description A randomised comparison of three triple combinations of antiretroviral agents including nevirapine in patients who are antiretroviral naive. Status enrolment closed December 98, follow-up continuing Sites same as OZCombo I Enrolled/target 73/120 Sponsor Glaxo Wellcome / Bristol-Myers Squibb / Boehringer-Ingelheim / NCHECR Contact Jeff Hudson, Sean Emery PIILR Description An open label, multicentre, randomised study of the reversibility of HIV-protease induced lipodystrophy in HIV-1 subjects. Status enrolment closed December 98, follow-up continuing Sites 15 Enrolled/Target 79/80 Sponsor Glaxo Wellcome / Boehringer-Ingelheim / Gilead Sciences / NCHECR Contact Jeff Hudson, DonSmith NATIONAL LIPODYSTROPHY SURVEY Description A national prevalence survey of lipodystrophic phenomena in patients with HIV. Status open - commenced November 1998 Sites 14 Enrolled/Target 300/1500 Sponsor Roche / Abbott / Bristol-Myers Squibb / NCHECR Contact John Miller 18

20 CHRN 025 Description A randomised, open label comparison of stavudine, SGC-saquinavir and delavirdine versus stavudine, SGC-saquinavir and ritonavir versus stavudine, SGC-saquinavir and nelfinavir in HIV positive, treatment experienced patients. Status opened September 1997, recruitment terminated Oct 98 Sites 27 Enrolled/Target 75/150 Sponsor NCHECR / Roche / Bristol Myers Squibb / Abbott / Pharmacia & Upjohn Contact Gillian Hales, Don Smith BI 1036 Description Long-term follow-up of nevirapine use in patients who participated in randomised trials of nevirapine. Status opened 1994, follow-up continuing Sites 1 Enrolled/Target 4/4 Sponsor Boehringer Ingelheim Contact Pat Grey, Don Smith GILEAD (GS98432) Description An international, multicentre, open label study of the safety and efficacy of adefovir dipivoxil in combination therapy for antiretroviral naive patients. Status open Sites 2 EnrolledTarget 4/8 Sponsor Gilead Contact Gillian Hales, Sean Emery HIVNAT (THAILAND) Description A randomised, open-label follow-up study to protocol HIV-NAT 001 to explore the antiretroviral efficacy and tolerability of ddi + d4t + saquinavir SGC vs. combivir + saquinavir SGC in an HIV-infected Thai population pretreated with AZT and ddc for at least 48 weeks. Status enrolment complete, follow up continuing Sites 1 Enrolled/Target 95/95 Sponsor HIVNAT / Bristol-Myers Squibb Thailand / Roche Thailand / NCHECR Contact Chris Duncombe, Sean Emery HIVNAT (THAILAND) Description A randomised, open-label study of the efficacy and tolerability of immediate vs deferred switching from ddi/d4t to AZT/3TC in a Thai HIV-1 infected population. Status enrolment complete, follow-up continuing Sites 1 Enrolled/Target 71/71 Sponsor HIVNAT / Bristol-Myers Squibb Thailand / Glaxo Wellcome Thailand / Thai Ministry of Public Health / NCHECR Contact Chris Duncombe, Sean Emery 19