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The Xpert HPV Test is used at point of care for cervical screening in a number of low and middle income countries (LMIC). It is validated for use with ThinPrep-PreservCyt transport medium which has a high methanol content and is therefore classified as a dangerous good for shipping, making cost, transportation and use challenging within LMIC. We compared the performance of ThinPrep against four non-volatile commercially available media for human papillomavirus (HPV) point of care testing. Ten-fold serial dilutions were prepared using three HPV cell lines each positive for 16, 18 or 31 and with each suspended in five different media types. The media types consisted of Phosphate Buffered Saline (ThermoFisher Scientific, USA), Sigma Virocult (Medical Wire and Equipment, UK), MSwab (Copan, Italy) Xpert Transport Media (Cepheid, USA) and ThinPrep-PreservCyt (Hologic, USA). A total of 105 Xpert HPV tests were conducted in a laboratory setting, with seven 10-fold dilutions of each of the three HPV genotypes tested in all five media types. The lowest HPV 10-fold dilution detected for any media, or cell line was the fifth dilution. MSwab was the only medium to detect HPV to the fifth dilution across all three cell types. MSwab transport media may be a suitable alternative to ThinPrep for Xpert HPV point of care testing. A field based, head to head comparison of both media types using the Xpert HPV assay is warranted to confirm these laboratory based findings., (Copyright © 2020 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

This study created a retrospective cohort by linking repeat respondents in a large, national, annual cross-sectional sero-survey to estimate HIV incidence among people who inject drugs (PWID) in Australia. The results indicate extremely low and sustained rates of HIV incidence (0.11 per 100 person-years) over almost two decades (1995-2012). The findings demonstrate that sustained prevention of HIV transmission among PWID is possible and suggest that the early establishment and rapid scale-up of needle and syringe programmes, at a time when background prevalence was low, likely contributed to the prevention of an HIV epidemic among Australian PWID.

Purpose of Review: To review recent studies reporting epidemiological and public health aspects of primary and recently acquired HIV infection, with a particular emphasis on patterns of occurrence, relationship to onward transmission, diagnostic strategies and risk factors., Recent Findings: Diagnosis of primary HIV infection remains a relatively infrequent occurrence. Clinical and demographic characteristics may be helpful indicators to guide the decision to offer testing. The high levels of viraemia associated with primary HIV infection represent a particular risk of onward transmission, as recently demonstrated through studies using genotyping methods to link newly acquired cases. Diagnostic strategies involving nucleic acid detection have been increasingly used to identify cases prior to the development of antibodies. Serological tests for early infection are valid for epidemiological purposes but are not generally viewed reliable enough for individual diagnosis. Prospective studies continue to be a useful means of identifying factors associated with the risk of newly acquired HIV infection, and can guide the implementation and evaluation of prevention strategies., Summary: The occurrence of primary HIV infection is an event of public health importance. Understanding of the extent of primary HIV infection and its risk factors in populations can guide the development and evaluation of preventive interventions.

Objective: To determine whether reporting that the HIV-positive partner's viral load is undetectable rather than detectable is associated with unprotected anal intercourse (UAI) in HIV serodiscordant gay couples., Method: A cross-sectional study nested within two cohort studies, the Health in Men (HIM) cohort of HIV-negative men, from July 2001 to December 2003 and the Positive Health (PH) cohort of HIV-positive men, from February 2002 to August 2003. The study participants were 119 men in an HIV serodiscordant regular relationship of at least 6 months duration (45 HIV-negative men from HIM, 74 HIV-positive men from PH). The main outcome measure was the occurrence of UAI within the relationship in the previous 6 months., Results: Eighty-two men reported no UAI and 37 reported some UAI. Of couples in which the HIV-positive partner's viral load was reported to be undetectable, 39.4% reported UAI compared with 20.8% of those where viral load was reported to be detectable (P = 0.04). In multivariate analysis, significant predictors of UAI were younger age [odds ratio (OR), 0.94; 95% confidence interval (CI), 0.87-1.00; P = 0.05], greater HIV optimism (OR, 4.98; 95% CI, 1.25-19.8; P = 0.02) and reported undetectable viral load (OR, 2.88; 95% CI, 1.13-7.37; P = 0.03)., Conclusions: Most serodiscordant gay couples do not engage in any UAI. UAI within such relationships is significantly more likely to occur where the HIV-positive partner is reported to have undetectable viral load. UAI in HIV serodiscordant relationships is problematic even if viral load is undetectable because of unknown risk parameters, viral load variability and the possibility of drug-resistant strains of HIV.

Background: Hypertriglyceridaemia is common in patients with HIV, especially those taking protease inhibitors or with lipodystrophy, frequently observed at levels associated with accelerated cardiac disease. This study aimed to explore the efficacy and safety of gemfibrozil for hypertriglyceridemia in patients with HIV infection., Methods: A 16-week, randomized, double-blind, comparative study of low saturated fat diet versus low saturated fat diet with gemfibrozil 600 mg twice daily in patients with triglycerides > or = 3mmol/l receiving protease inhibitor therapy. Following a 4-week period of dietary intervention alone, patients were randomized to gemfibrozil or matching placebo. The primary outcome was the difference in mean change in fasting triglycerides at week 16 between the two groups., Results: 37 men were randomized (17 gemfibrozil, 20 placebo) with median fasting triglycerides 5.6 mmol/l. Mean changes in triglycerides from week 4 to week 16 were -1.22 mmol/l and +0.35 mmol/l for the gemfibrozil and placebo groups respectively (between-group mean difference of 1.57 mmol/l; 95% confidence interval, -6.7 to 3.5; = 0.08). Only one patient treated had triglycerides return to a desirable range (< or = 2.00 mmol/l). No significant changes in the other metabolic parameters were observed. Gemfibrozil was well tolerated, did not appear to induce additional protease inhibitor toxicity, and did not induce changes in CD4 lymphocyte counts or HIV RNA load., Conclusions: Gemfibrozil is safe and demonstrated at most, modest efficacy for hypertriglyceridemia in HIV-infected patients receiving protease inhibitors. Given the level of response, however, it is unclear whether these reductions will confer clinical benefit, at least in the presence of continued protease inhibitor use.

Objective: To describe the changing incidence of Kaposi's sarcoma (KS) and non-Hodgkin's lymphoma (NHL) in people with HIV in Australia during the time period of introduction of potent combination anti-retroviral therapy., Design: A national, population-based linkage study of cancer and HIV registration data., Methods: We calculated person-year rates of KS and NHL in people after reporting of HIV diagnosis. Trends in cancer incidence rates were examined, based on four time periods defined by the availability of specific anti-retroviral therapies., Results: Linkage identified 206 cases of KS and 235 cases of NHL in 8108 people reported with HIV infection. There was an increasing trend in NHL incidence rates over the four time periods (P for trend, 0.012), but incidence for the period since the availability of the new therapies was significantly lower than that for the period immediately prior (incidence rate ratio 0.58; 95% confidence interval, 0.36-0.92). Incidence of KS had been decreasing prior to the new therapies and declined further since their widespread use (P for trend, 0.045)., Conclusions: Population-based incidence rates of AIDS related KS and NHL have decreased since the widespread use of potent anti-retroviral therapies in Australia. NHL incidence decreased less than KS, and NHL is now the most common AIDS-associated cancer in Australia.

Objectives: To determine the protective efficacy of highly active antiretroviral therapy (HAART) against AIDS dementia complex (ADC) relative to other initial AIDS-defining illnesses (ADIs), Australian AIDS notification data over recent years were examined., Methods: All initial ADIs in Australia over the period 1992-1997 were included. Three initial ADI groups were established: ADC; other predominantly central nervous system (CNS) ADIs (toxoplasmosis and cryptococcosis); and non-CNS ADIs. For each ADI grouping, the proportion of total ADls, and median CD4 cell count in the pre-HAART era (1992-1995) were compared with the HAART era (1996 and 1997)., Results: Initial ADls peaked in Australia in 1994 (n = 1049), with a gradual decline to 1996 (n = 722), and a marked decline in 1997 (n = 367). ADC constituted 4.4% of initial ADIs over the period 1992-1995, but increased after the introduction of HAART to 6.0% in 1996 and 6.5% in 1997 (P = 0.02). In contrast, the proportion of other CNS ADIs (1992-1995, 8.1%; 1996, 6.0%; 1997, 8.2%; P = 0.41) was stable over the period 1992-1997. The median CD4 cell count at ADC diagnosis increased from 70/mm3 in 1992-1995 to 120/mm3 in 1996 and 170/mm3 in 1997 (P = 0.04). Although the median CD4 cell count also increased significantly over this period for both other CNS ADIs (40-60/mm3; P = 0.02), and non-CNS ADIs (60-70/mm3; P = 0.02), the increase was small., Conclusion: A proportional increase in ADC compared with other ADIs and a marked increase in the median CD4 cell count at ADC diagnosis have occurred since the introduction of HAART in Australia. These changes suggest that HAART has a lesser impact on ADC than on other ADIs, with the poor CNS penetration of many antiretroviral agents a possible explanation.

Objectives: To determine whether the incidence of cancers other than the AIDS-defining cancers is increased in people with AIDS, and to determine if cancer incidence increases with time, a surrogate marker of declining immune function., Design: Register-based retrospective cohort study in New South Wales, Australia. Age-, sex-, and period-adjusted standardized incidence ratios (SIR) were calculated for individual cancers occurring in 1980-1993 in people with AIDS registered before 1996., Results: During the study period, 3616 people were registered with AIDS; 716 cases of AIDS-defining cancer and 62 cases of non-AIDS-defining cancer were identified. People with AIDS had a significantly increased incidence of Hodgkin's disease [SIR 18.3; 95% confidence interval (CI) 8.39-34.8], multiple myeloma (SIR 12.1; 95% CI 2.50-35.4), leukaemia (SIR 5.76; 95% CI 1.57-14.7), lip cancer (SIR 5.94; 95% CI 1.92-13.8) and lung cancer (SIR 3.80; 95% CI 1.39-8.29). The incidence of Hodgkin's disease increased significantly around the time of AIDS diagnosis (P = 0.008 for trend with time), suggesting an association with immunodeficiency., Conclusions: This study provides strong support for the hypothesis that Hodgkin's disease is an AIDS-associated condition. There was an increased incidence of several other forms of cancer, some of which are known to occur at increased rates in transplant recipients who have received immunosuppressive therapy. Improved survival in people with HIV infection may lead to increases in the number that develop these forms of cancer.

We examined sexual behavior as a risk factor for Kaposi's sarcoma-associated herpesvirus (KSHV) infection and examined the relation between KSHV seropositivity and development of KS in cross-sectional and cohort studies of 130 homosexual men diagnosed with AIDS in Sydney, Australia during the period from 1991 to 1993. KSHV serology was measured using antibody tests to latency-associated nuclear antigen (LANA) and lytically expressed open reading frame (ORF) 65.2. In the cross-sectional analysis, 52% (68) of study subjects were KSHV-seropositive by either assay. KSHV-seropositive men were significantly more likely to be seropositive to both herpes simplex type 2 (odds ratio [OR] 3.0; 95% confidence interval [CI], 1.2-7.5 for LANA and OR 2.8; 95% CI, 1.3-6.0 for ORF 65) and hepatitis A virus (OR 2.2; 95% CI, 1.1-4.5 for ORF 65). KSHV-seropositive men reported nonsignificantly more casual sexual partners and were nonsignificantly more likely to report insertive oroanal contact with casual partners. These data suggest that KSHV might be sexually transmitted among homosexual men. Men were observed until October 1996 for development of KS. Those seropositive to either KSHV assay at baseline were more likely than the seronegative to develop KS during follow-up (rate ratio [RR] 4.4; 95% CI, 1.9-10.2). Of those seropositive for KSHV, 53% developed KS.

Objectives: To assess whether AIDS cases in Australia have been diagnosed at higher CD4 counts since the widespread availability of highly active antiretroviral treatment (HAART) in mid-1996., Methods: Data on the CD4 count at AIDS diagnosis for AIDS cases diagnosed between 1 January 1992 and 31 December 1997, and reported to the National AIDS Registry in Australia by 31 March 1998, were analysed. The median CD4 count at AIDS diagnosis, and the proportions of AIDS diagnoses with a CD4 count above 100 cells/microl, and above 200 cells/microl, were calculated by the year of diagnosis, both for all AIDS-defining illnesses, and for each illness separately. Analyses were also stratified by the time interval between HIV and AIDS diagnoses (less than or equal to, or more than, 3 months) because people diagnosed with HIV close to the diagnosis of AIDS would generally not have received any antiretroviral treatment before the diagnosis of AIDS, and so no trends in CD4 counts at the diagnosis of AIDS would be expected in this group., Results: There was an increase in CD4 count at AIDS diagnosis in 1996 and 1997, although this increase was only apparent for AIDS-defining illnesses other than Pneumocystis carinii pneumonia (PCP), and was limited to AIDS cases diagnosed with HIV more than 3 months before AIDS. In cases of AIDS other than PCP, and diagnosed with HIV more than 3 months before AIDS, the median CD4 count increased from 50 cells/microl in 1995 to 80 cells/microl in 1996 and 134 cells/microl in 1997., Conclusions: There has been an increase in the CD4 count at AIDS diagnosis for most AIDS-defining illnesses in Australia coincident with the widespread availability of HAART.

Objective: To investigate the significance of the time from seroconversion to AIDS (incubation time) and other covariates for survival from AIDS to death., Methods: In survival analysis, survival from AIDS to death was compared for different categories of length of incubation time adjusted and unadjusted for other covariates, and significant predictors for survival from AIDS to death were investigated., Results: Survival after AIDS was not affected by the incubation time in univariate as well as in multivariate analyses. Predictive factors for progression from AIDS to death were age at seroconversion, type of AIDS diagnosis, and CD4 cell count at AIDS. The relative hazard for age at seroconversion increased 1.38-fold over 10 years. Men with a CD4 cell count at AIDS of <130 x 10(6)/l had a twofold higher risk in progression to death than men with higher CD4 cell counts. Persons diagnosed with lymphoma had a sixfold higher risk of progression to death than persons with Kaposi's sarcoma or opportunistic infections., Conclusions: The incubation time as well as other factors before AIDS did not affect survival after AIDS. Survival from AIDS to death can be predicted by data obtained at the time of AIDS diagnosis, such as type of diagnosis, age and CD4 cell count. AIDS seems to be a significant point in progression to death, and not just a floating point between infection and death affected by prior factors for persons who did not receive effective therapy and did not have long incubation times.

DNA adducts formed by cisplatin [cis-diamminedichloroplatinum(II)] were measured in blood samples from 48 testicular cancer patients treated in four centers in Europe during four to six cycles with cisplatin infusions on five successive days (total samples, 112). Total protein-bound platinum (Pt) in blood was also measured (total samples, 84). The mean on the main DNA adduct, cis-Pt(NH3)2d(pGpG) (Pt-GG), was 0.75 fmol/microg DNA [standard deviation (SD) = 0.66] on the first day of the first cycle, increased after the infusion at day 5 of the cycle (mean 1.74 fmol/microg DNA, SD = 0.90) and decreased on the following day (mean 1.09 fmol/microg DNA, SD = 0.62). In subsequent cycles, there was a tendency to an increase in the mean Pt-GG levels. The values of protein-bound Pt in blood showed little reduction between day 5 and 6 of each cycle, and a stable increase during the course of the therapy. Strong correlations were seen between day 1, 5 and 6 of the first cycle for both Pt-GG and protein-bound Pt in blood. A strong correlation (r = 0.62, p < 0.001, 69 pairs) was found between the levels of Pt-GG and protein-bound Pt. Only two patients relapsed during the follow-up; therefore, the analysis of the association between Pt-GG levels and response to therapy was not informative. The results of this study suggest that DNA adducts formed by cisplatin at the beginning of chemotherapy are predictive of values found during later days and cycles, and that the value of protein-bound Pt in blood is predictive of the value of DNA adducts.

Objective: To estimate time trends in HIV prevalence among pregnant women delivering livebirths in 14 European countries using a uniform methodology., Methods: A form of back-projection was used to estimate HIV prevalence among pregnant women based on reported cases of AIDS due to perinatally acquired HIV infection. The method used estimates the rate of progression to AIDS in children with HIV, and the rate of transmission of HIV from mother to child, derived from published studies., Results: The prevalence of HIV among pregnant women delivering livebirths was estimated to be highest in Spain (2.61 per 1000 livebirths in 1992-1993), relatively high (> or = 0.3 per 1000 livebirths) throughout the period 1984-1993 in France, Italy and Switzerland, and low (< 0.2 per 1000 livebirths) in Germany, The Netherlands and Scandinavia. There were large and statistically significant increasing trends in the estimated HIV prevalence among pregnant women in Portugal (an estimated 77% increase per 2-year period), Spain (40% increase) and the United Kingdom (77% increase; all P < 0.001). Statistically significant increasing trends of a smaller magnitude were estimated for France (24% increase) and Italy (23% increase; both P < 0.001)., Conclusions: Sharp increases in HIV prevalence among pregnant women were estimated for several European countries, whereas in other countries no trends in the estimated prevalence were detected.

Background: The beta-chemokine receptor CCR-5 is used as a coreceptor by macrophage-tropic strains of HIV-1 to gain entry into CD4+ cells., Objective: To determine the effect of a common 32 base-pair deletion mutation in the CCR-5 gene (CCR-5 delta 32) on progression of HIV infection to AIDS, and to assess the level of heterozygosity for this mutation in a well-defined group of long-term non-progressors (LTNP)., Participants: Sixty-four HIV-1-infected LTNP (CD4+ T lymphocyte count > 500 x 10(6)/l after 8 years) were compared with 95 individuals infected within a similar period (1983-1986) but who had rapidly progressed to AIDS and death, and with a further 120 HIV-positive individuals with CD4+ counts < 500 x 10(6)/l., Methods: The presence of the CCR-5 delta 32 mutation was assessed using polymerase chain reaction with primers spanning the 32 base-pair deletion. CD4+ and CD8+ counts, plasma HIV-1 RNA, p24 antigen and beta 2-microglobulin levels in LTNP carrying the CCR-5 delta 32 mutation were compared with LTNP lacking the mutation., Results: A marked increase in the frequency of CCR-5 delta 32 heterozygosity was found among LTNP (35.9%) compared with rapid progressors (12.6%; P = 0.0005) and patients selected on the basis of a CD4+ T-cell count < 500 x 10(6)/l (12.5%; P = 0.0004). LTNP heterozygous for CCR-5 delta 32 had a significantly higher CD8+ T-cell count than those without the mutation (1218 versus 972 x 10(6)/l; P = 0.044). No significant correlation was observed between heterozygosity and CD4 count, viral load, p24 antigen or beta 2-microglobulin within the LTNP group., Conclusions: This study provides the strongest evidence to date for the importance of a single copy of the CCR-5 delta 32 mutation in long-term non-progression of HIV infection, which may involve, in part, CD8+ T lymphocytes.

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).

To characterize the associations of age, immunosuppression, and AIDS outcomes, we evaluated serial measures of CD4+ lymphocytes from 376 homosexual men with documented dates of HIV-1 seroconversion registered in the Tricontinental Seroconverter Study. Using regression models and adjusting for variation within individuals, we found no association between age and the number of CD4+ lymphocytes at seroconversion or with CD4+ lymphocyte decline after seroconversion. Men who developed opportunistic infections had fewer CD4+ lymphocytes at the time of diagnosis compared with men who developed AIDS-defining Kaposi's sarcoma. Older age was significantly associated with higher numbers of CD4+ lymphocytes in individuals diagnosed with AIDS-defining Kaposi's sarcoma but was not significant for individuals with opportunistic infections. Because older age shortens the latency period of Kaposi's sarcoma and does not affect the CD4+ lymphocyte loss, it results in higher CD4+ lymphocytes at the time of diagnosis. These findings suggest distinct biologic mechanisms for various AIDS manifestations, which is important for clinical decision making and health care planning.

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.

Objective: To reconstruct past HIV-1 incidence and identify risk factors for HIV-1 seroconversion among female commercial sex workers in a semi-rural setting in northern Thailand., Design: Retrospective cohort of sex workers attending a sexually transmitted disease (STD) clinic at Mae Chan District Hospital, Chiang Rai Province, Thailand., Methods: Information included demographic data, HIV-1 antibody testing and STD diagnosis was collected in 821 sex workers attending the STD clinic from 1989 through 1993. HIV-1 incidence among initially HIV-1-seronegative sex workers who underwent repeat HIV-1 antibody testing during follow-up was determined and possible predictive factors for seroconversion including diagnosis of other STD were examined., Results: HIV-1 seroprevalence among 556 sex workers who underwent antibody testing was 52%, rising from 29% at initial test in 1989 to 53-63% for 1990-1993. Among 96 initially HIV-1-negative sex workers who underwent repeat testing, 64 HIV-1 seroconversions occurred, giving an incidence rate of 12.6/100 person months (PM). Incidence increased from 12.0/100 PM for 1989 and 1990 to 17.0/100 PM for 1991, with a subsequent decline to 9.3/100 PM for 1992-1993. The cumulative risk of seroconversion 6 months following initial negative HIV-1 antibody test was 57%. There were higher rates among younger sex workers (14-19 years old) and those from Hilltribes, but only a diagnosis of chancroid was significantly associated with HIV-1 seroconversion (P = 0.014)., Conclusion: An explosive epidemic of HIV-1 occurred among sex workers in a semi-rural area of northern Thailand from 1989. These HIV-1 incidence estimates, which are among the highest rates of sexual transmission ever reported, highlight the extreme vulnerability of female sex workers to HIV infection, even in a non-urban setting.

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.

Estimates of the lifetime cost of illnesses are needed for temporal and international comparisons and for assessment of the efficiency of prevention strategies. The goal of the present study was to estimate the average present value, at both the time of diagnosis and the time of seroconversion, of the lifetime cost of health care for HIV infection. Australian data on the monthly cost of HIV-related health care for homosexual men were linked with published data on disease progression using survival analysis methods. Future costs were discounted at 5% per annum. For a patient diagnosed when his CD4+ count fell below 500 x 10(6)/L, the average present value in 1992-1993 of lifetime cost was approximately $93,000, of which 49% was for drugs and 32% was for hospital bed-days. For a man infected in 1992-1993 and diagnosed when his CD4+ count falls below 500 x 10(6)/L, the average present value of lifetime cost at the time of seroconversion is approximately $70,000. These estimates are lower than the lifetime cost of $119,000 reported recently in the United States. However, when the U.S. figure was adjusted to make discounting of future costs consistent between the two studies, lifetime costs were approximately 17% lower in the United States. The lower American costs appear to be due to lower rates of hospitalization and drug prescribing, possibly because of reduced access to health services, but underestimation of costs due to study methodology might also explain the difference.

Objective: To investigate a possible outbreak of tuberculosis in an outpatient HIV treatment facility in Sydney, Australia., Design: Following the diagnosis of pulmonary tuberculosis in an attendee, a prospective screening program was instituted to investigate the potential outbreak., Methods: Screening of 89 potentially exposed patients included chest radiographs (n = 89), and sputum examination (n = 37) over a period of 23 weeks., Results: No cases of tuberculosis were detected by the screening program. However, three (3.4%) of this cohort developed pulmonary tuberculosis between 8 and 10 weeks following diagnosis of the index case. The incidence of active tuberculosis during the following-up period (median, 7.4 months) was 5.3 per 100 person years and represents the lower limit of possible tuberculous infection, as both latent infection, and undiagnosed tuberculosis among those who died could not be excluded. Mycobacterium tuberculosis strains isolated from the index case and three subsequent cases were found to be identical by DNA typing., Conclusion: Nosocomial transmission of tuberculosis in an outpatient treatment setting has been demonstrated. The risk of nosocomial transmission of tuberculosis is significant in institutions caring for HIV-infected patients even in countries with a low prevalence of tuberculosis infection, and highlights the importance of adherence to tuberculosis control guidelines.

Objective: To describe patterns of health-service usage and the resulting costs in 1992-1993 for Australian men., Design: A prospective survey, stratified by phase of illness., Setting: Hospital and community-based care., Patients: A total of 128 homosexual men: 20 in phase 1 (CD4+ count > or = 500 x 10(6)/l), 31 in phase 2 (CD4+ count < 500 and > or = 200 x 10(6)/l), 30 in phase 3 (CD4+ count < 200 x 10(6)/l), and 47 in phase 4 (AIDS)., Main Outcome Measures: Mean monthly service usage rates and costs., Results: Health-service utilization increased and became more hospital-based as illness worsened; the main exception was use of antiretroviral drugs, which peaked in phases 2 and 3. Hospital admission was rare before diagnosis of AIDS. Hospital bed-days per patient per month averaged 3.3 for AIDS patients until the final 3 months of life increasing to 15.8 in the 3 months before death. Mean monthly costs (in 1992-1993 Australian dollars) were $331 [95% confidence interval (CI), 218-455] in phase 1, $667 (95% CI, 540-836) in phase 2, $1372 (95% CI, 1044-1776) in phase 3, and $4615 (95% CI, 3456-5985) for AIDS patients until the last 3 months of life and $13,308 (95% CI, 10,538-16,516) in the 3 months before death. Drugs comprised 57% of total costs in phase 1, but only 30% of costs for patients with AIDS, whereas hospital bed-days comprised 10% of phase 1 costs and 60% of AIDS costs., Conclusions: Health-care utilization and resulting costs increased with severity of illness, and were particularly high for AIDS patients in the 3 months before death. Service-utilization patterns and components of costs varied between each phase.

Objective: To examine the role of initial AIDS-defining illness in survival following AIDS and survival trends over time., Design: States and Territory Health Departments notified new diagnoses of AIDS to the National AIDS Registry. Information on vital status and date of last medical contact was sought annually., Methods: Survival was calculated for all adult and adolescent AIDS cases (n = 3204) in Australia diagnosed until 1 November 1991 and reported to the National AIDS Registry by 31 March 1994. The Cox regression method was used to identify independent predictors for survival., Results: Age < 50 years, a CD4+ cell count > or = 100 x 10(6)/l and an initial diagnosis of Kaposi's sarcoma were independently associated with longer survival (P < 0.05). Acquisition of HIV through blood transfusion and the AIDS-defining illness non-Hodgkin's lymphoma were significantly associated with shorter survival. Survival improved substantially from 1986 to 1987, but did not improve further thereafter. A further study of initial AIDS-defining illnesses in a subgroup of individuals, i.e., men aged < 50 years at diagnosis who acquired HIV infection through homosexual or bisexual contact and diagnosed after 1987, showed that Kaposi's sarcoma, Pneumocystis carinii pneumonia, oesophageal candidiasis and herpes simplex virus as initial AIDS-defining illnesses had a relatively better prognosis than other single illnesses. Furthermore, patients with multiple illnesses did not have a worse prognosis than patients with a single illness, provided all illnesses were those with a better prognosis., Conclusions: Initial AIDS-defining illness, as well as age at diagnosis, year of diagnosis, HIV exposure and CD4+ cell count at diagnosis, plays an important role in survival following AIDS in Australia.

Objective: Accurate estimates of HIV incidence that reflect the effect of non-vaccine interventions (education, counselling, condom promotion, and possibly sexually transmitted disease treatment) and that may be provided in a Phase III vaccine efficacy trial, are needed so that vaccine trial population sample sizes can be accurately determined. In order to avoid delays in the implementation of efficacy trials, well characterized cohorts must also be developed and available to participate in such trials. We reviewed the potential study populations, the epidemiologic methods for the determination of HIV incidence (using open cohort, closed cohort, and seroprevalence data methods), and the need for the development of population cohorts in preparation for Phase III HIV vaccine efficacy trials., Setting: Phase III trials in developed and developing countries., Methods: Comparison of open and closed cohorts and those using seroprevalence data to estimate HIV incidence., Results: Open and closed cohorts each have disadvantages and advantages. However, the open cohort may be more suitable for determining estimates of HIV incidence that reflect non-vaccine interventions and for the development of a well characterized cohort available to participate in efficacy trials., Conclusion: Careful preparation of research infrastructures and population cohorts will help ensure the successful conduct of scientifically and ethically sound HIV vaccine efficacy trials in the future.

Objective: To further examine the hypothesis that Kaposi's sarcoma (KS) among people with AIDS is caused by a sexually transmissible infectious agent., Design: Analysis of Australian AIDS surveillance data for the period 1982-1991 by sex, age, exposure category, country of birth, year and place of diagnosis., Main Outcome Measures: Percentage of people with AIDS who had KS., Results: In Australia, by November 1991, 17.2% (527 out of 3067) of individuals with AIDS aged > or = 13 years had presented with KS as their AIDS-defining illness: men, 17.6% (524 out of 2977); women, 3.4% (three out of 87) (P < 0.001). KS was predominantly reported in people aged 20-49 years and there were no cases in children < 13 years of age. In general, KS was more common in those who had acquired HIV by sexual contact rather than parenterally. Among people aged > or = 13 years, the proportion with KS ranged from 0.0% (none out of 41) in men with haemophilia to 1 Iford 9.0% (483 out of 2542) in men reporting homosexual contact. Between 1984-1985 and 1990-1991, the percentage of men with AIDS reporting homosexual contact who presented with KS declined from 30% (37 out of 124) to 15% (145 out of 995) (chi 2 for a linear trend, P < 0.001). For men with AIDS reporting homosexual contact, the percentage with KS in New South Wales and Victoria (20.3%) was higher than in the other States and Territories (12.5%) (P < 0.001). New South Wales and Victoria have also reported the highest incidence of AIDS in Australia., Conclusion: The epidemiological characteristics of KS among people with AIDS in Australia are broadly consistent with those reported from the United States and Europe. This provides further evidence that KS may be caused by a sexually transmissible infectious agent. The nature of the infectious agent and its mode of transmission have yet to be determined.

Objective: To determine the rate of development of AIDS, and the demographic and clinical cofactors for development of AIDS in a group of 117 people with transfusion-acquired HIV infection, who were infected between 1980 and 1985 in New South Wales, Australia., Results: By December 1991, 67 (57%, 95% CI 48-66%) of the study subjects had developed AIDS. The estimated median time to development of AIDS was 7.2 years from the date of infection. There was no significant difference in median age at infection or sex between individuals who did and did not develop AIDS. The median time to development of AIDS was shorter in older individuals (median time to AIDS for age groups 13-39, 40-59 and > 59 was 7.8, 7.1 and 5.4 years, respectively; P = 0.20). A significantly greater proportion of individuals who had never received treatment with zidovudine developed AIDS compared with individuals who had (P = 0.04). But in a statistical analysis which took account of the changing availability of zidovudine over time, there was no significant association between the development of AIDS and treatment with zidovudine (P = 0.44)., Conclusion: Consistent with other studies, age appeared to increase the rate of progression to AIDS, although not significantly so in this study.