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Objective: To characterize the associations of age and progression rates to AIDS-defining neoplasms and opportunistic infections (OI) in HIV-infected homosexual men., Methods: Data from 407 homosexual men with documented dates of HIV seroconversion participating in cohort studies from four geographic locations were merged. Kaplan-Meier and Cox proportional hazards analyses were conducted with respect to the association of age with time from seroconversion to the first AIDS-defining neoplasm and OI., Results: Among the 407 participants, 139 (34%) were diagnosed with AIDS; 45 (11%) with neoplasms and 90 (22%) with OI. Older age at seroconversion was significantly associated with faster progression to neoplasms, but not to OI. For each 10-year increase in age the risk for neoplasms increased 1.65-fold [95% confidence interval (CI), 1.12-2.43], after adjustment for clinical treatments. For OI this risk estimate was 0.98 (95% CI, 0.72-1.34)., Conclusions: Increasing age is associated with faster progression to AIDS-defining neoplasms, but not with progression to OI. This has not been previously reported and may explain conflicting results in other studies among homosexual men that considered AIDS as a single entity. Our findings suggest that age and AIDS manifestations should be considered, particularly in the context of natural history studies, clinical trials and mathematical modelling.

Objectives: To investigate (1) the efficacy and safety of zidovudine treatment in homo-/bisexual men with AIDS-related complex (ARC) and (2) factors associated with development of intolerance to zidovudine., Design: A multicentre open-label study., Setting: Australian public hospital system., Subjects: A total of 235 homo-/bisexual men with ARC were enrolled., Interventions: All subjects received 1200 mg zidovudine daily., Main Outcome Measures: Survival, incidence and time to development of AIDS and to development of haematological and clinical side-effects., Results: Median time to development of AIDS was 61 weeks, significantly longer (P < 0.03) than the median of 22 weeks in a small control group of 12 untreated ARC subjects. Median survival from development of AIDS was 48 weeks, marginally longer than the 44 weeks in untreated historical AIDS controls. Anaemia requiring transfusion occurred in 113 subjects (48%). Significant differences in time to development of AIDS were found in favour of subjects not requiring transfusions (P < 0.001) with no weight loss (P = 0.004), and who received the full zidovudine dose (1200 mg) during the first 52 weeks of treatment (P = 0.021). Significantly longer median survival times from commencement of zidovudine were found in subjects with a baseline Karnofsky score > or = 90, baseline Hb > or = 13 g/dl, baseline CD4+ cell count > or = 50 x 10(6)/l, no weight loss during first year of treatment, and no or not more than one blood transfusion during treatment. The ability to tolerate full-dose zidovudine was best predicted by a baseline Hb > or = 13 g/dl. Zidovudine-intolerant subjects (defined as the development of either anaemia requiring transfusions, WCC 1000 x 10(6)/l or zidovudine-related myopathy) had a significantly shorter time to development of AIDS than zidovudine-tolerant subjects (P = 0.002)., Conclusions: Zidovudine may benefit people with ARC by significantly postponing the development of AIDS. This benefit appears to be greater in those who do not develop clinical intolerance whilst receiving zidovudine. However, administration of zidovudine to subjects with ARC does not appear to contribute to improved survival after the development of AIDS. People with ARC who develop AIDS while receiving zidovudine, or who develop intolerance to zidovudine, should be considered immediately eligible for other antiretroviral therapies.

Objective: To evaluate the decline in CD4+ counts in relation to the incidence of AIDS in different cohorts of homosexual men and to quantify possible consequences of laboratory variation in CD4+ measurement., Methods: Our study includes 403 men with well documented dates of HIV seroconversion originating from five cohort studies among homosexual men. Differences in time from HIV seroconversion to the first CD4+ count dropping < 500 or 200 x 10(6)/l and to AIDS were evaluated using Kaplan-Meier survival analyses., Results: We found considerable differences between cohorts in CD4+ depletion, but not in the incidence of AIDS (1987 definition)., Conclusions: Variation in CD4+ depletion appears to be mainly the result of laboratory differences. Policy recommendations on a basis of CD4+ counts probably requires a calibration of measurement. The 1993 AIDS case definition leads to a site-specific shortening of the incubation time, which complicates the study of the natural history of HIV infection and of trends in the AIDS epidemic.

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.

Objective: To determine whether HIV could be identified in semen samples during the first few weeks after infection., Design: A series of three homosexual men with symptomatic primary HIV-1 infection., Methods: Each subject provided a series of semen samples that was examined for HIV-1 by virus culture, polymerase chain reaction (PCR) and transmission electron micrography., Results: The first samples obtained for each subject (17, 22 and 24 days following onset of primary HIV-1 infection) were all positive by PCR and negative by viral culture. Of 13 samples obtained during the first 80 days after onset of primary HIV-1 infection and analysed by PCR, 10 were positive. Only one of these samples was virus culture-positive. Four semen samples obtained from two subjects during treatment with zidovudine were PCR-positive. Eight samples were examined for presence of HIV-1 by electron microscopy and one was found to be positive., Conclusions: These results indicate that men with HIV-1 infection are potentially infectious through sexual transmission during the first few weeks after infection. The findings emphasize that individuals in all stages of HIV-1 infection should practise safer sex to reduce transmission of HIV-1.

Objective: We compared the efficacies of low-dose trimethoprim-sulphamethoxazole (TMP-SMX; one tablet: TMP, 160 mg, SMX, 800 mg, twice daily, twice a week) and aerosolized pentamidine (300 mg every 4 weeks) as secondary prophylaxis against Pneumocystis carinii pneumonia (PCP) in patients with HIV infection., Design: A retrospective controlled study., Setting: The study was performed at St Vincent's Hospital, Sydney, Australia, which is a tertiary referral university hospital., Patients, Participants: Over a 4-year period, following primary episodes of PCP, 60 patients received TMP-SMX and 73 aerosolized pentamidine. Thirty-eight patients who received no secondary prophylaxis served as historical controls., Main Outcome Measures: The rate of and time to PCP relapse was recorded for patients receiving low-dose TMP-SMX, aerosolized pentamidine, or no prophylaxis., Results: Only one (1.7%) patient in the TMP-SMX-treated group relapsed, compared with 31 (42.5%) of those in the aerosolized pentamidine group and 21 (55.1%) of those in the control group (P less than 0.0001). Median PCP-free survival times were greater than 1153 days in the TMP-SMX group, 496 days in the pentamidine group, and 265 days in the control group (P less than 0.0001 between all groups). The rate of or time to relapse was not influenced by CD4+ lymphocyte count at the start of prophylaxis, primary therapy of PCP, history of allergy to TMP-SMX, or zidovudine therapy during the period of secondary prophylaxis in any patient group. Both therapies were well tolerated, with three (5%) of those receiving TMP-SMX and four (5%) of those receiving pentamidine discontinuing therapy as a result of side-effects., Conclusions: Low-dose TMP-SMX appears to be more effective compared with aerosolized pentamidine as secondary prophylaxis against PCP in HIV-infected patients. Zidovudine was well tolerated by both groups, but did not influence the rate of or time to relapse.

Eleven subjects who presented with a clinical illness characteristic of primary HIV-1 infection were treated with 1 g zidovudine daily for a median period of 56 days (range, 28-111 days). Primary HIV-1 infection was confirmed in each subject by seroconversion and virus isolation. The acute phase of the illness resolved a median of 4 days (range, 3-14 days) from commencement of zidovudine. Six subjects reported symptoms that may have been side-effects of zidovudine, the most common being nausea in four subjects and headache in two. Treatment was discontinued in one subject who had persistent headache and nausea. Haemoglobin, haematocrit and erythrocyte counts decreased and mean corpuscular volume increased significantly during the treatment. None of the subjects developed anaemia and none required dose modification or blood transfusion as a result of haematological side-effects. There were no significant differences in the granulocyte count or the lymphocyte count during any week of treatment when compared with baseline levels. There were no significant differences in T-cell subset numbers of the subjects during treatment compared with a group of historical controls. HIV-1 was isolated from several subjects during and after termination of zidovudine treatment. The results of this investigation indicate that zidovudine is a safe drug to administer to people with primary HIV-1 infection. There was no clear evidence, however, of any clinical benefit in terms of resolution of the acute illness and no indication that the treatment would prevent development of persistent infection.(ABSTRACT TRUNCATED AT 250 WORDS)

To determine the relationships between individuals' baseline T-cell subsets, their rates of change with time, and AIDS-free survival time, data were collected at 6-monthly intervals from 379 HIV-seropositive homosexual Sydney men, of whom 31 developed AIDS during the 3-year observation period. Both CD4% and rate of change of CD4% in an individual had significant prognostic value in determining AIDS-free survival time. Compared with subjects whose CD4% remained stable, subjects whose CD4% dropped by 7% or more in a year had a relative hazard of 35.1 (95% confidence interval = 11.7-105.6, P less than 0.001) of developing AIDS. Increasing CD4% had a significant protective effect, reducing the risk of developing AIDS. CD4%, CD4 cell count and CD4: CD8 ratios showed steeper declines in subjects who were later diagnosed with AIDS than in those who remained AIDS-free. The rates of immunological change in AIDS-free seroconverters and seropositives were similar, despite indeterminate differences in durations of infections. In the multivariate Cox regression analysis, baseline CD4%, the rate of change of CD4%, and baseline lymphocyte count were associated with AIDS-free survival time. Baseline CD4% had greater prognostic value than baseline CD4 cell count. Baseline CD8%, baseline CD8 count, their rates of change and their mean square errors were not independently significant in this analysis. These findings are important for clinicians monitoring HIV infection in an individual and for entry criteria and monitoring procedures in clinical trials. They also have implications for resource-poor settings; prognosis based on CD4% can be made with a flow cytometer without a full blood count.(ABSTRACT TRUNCATED AT 250 WORDS)

Three cases of oesophageal candidiasis in association with primary HIV infection are described. In each case the candidiasis was associated with a decreased number of circulating CD4+ cells and responded well to treatment with ketoconazole. Clinicians should be aware that severe opportunistic infections may develop during this stage of infection, presumably as a result of transient immunodeficiency. We argue that the definition of primary HIV infection should be extended to include severe opportunistic infections and neurologic presentations.