The cost of health care for HIV-positive patients.

Utilizing a prospective study of health service activity for HIV/AIDS, 2 estimates of hospital costs of care analysed with reference to gender, risk activity, immunological and clinical staging (1987 definition of AIDS) were undertaken. Utilizing combined costs per life year (based on hospital and hospice activity but not primary and community care) the ratio of costs for CD4 < 200 and CD4 > 200 was for most risk groups between 2-5:1 whilst for AIDS: pre-AIDS it was between 3.6-8.3:1 except for homosexuals where it was 12.6:1. A comparison of the standard hospital costs for infectious diseases with the published accounts for clinical AIDS care in Lothian suggests a 3-4-fold underestimate in the costs of providing a comprehensive health care service.

Progression of HIV: follow-up of Edinburgh injecting drug users with narrow seroconversion intervals in 1983-1985.

OBJECTIVE: To describe progression and survival of individuals infected with HIV by injecting drug use in Edinburgh. DESIGN AND METHODS: From 313 HIV-infected patients with retrospectively estimated narrow seroconversion intervals, 260 infected via injecting drug use in the years 1983-1985 were selected for the study group. MAIN OUTCOME MEASURES: The effects of gender, age, human leukocyte antigen (HLA) type and zidovudine (ZDV) treatment on progression and survival from seroconversion; Weibull estimates of the AIDS incubation distribution and the overall survival distribution; slopes of absolute CD4 lymphocyte loss (on the square root scale) and loss of CD4 percentage. RESULTS: The cumulative progression rates at 10 years were 68% to CDC stage IV and 31% to AIDS with a mortality rate of 25%. Three-year survival rates for AIDS and CDC stage IV cases were 25 and 72%, respectively. Gender and age effects on progression or overall survival were not found, although those aged over 30 years experienced poorer survival from AIDS. A strong HLA (A1, B8, DR3) association with faster progression and poorer survival was found. Median survival was estimated by Weibull distribution to be 12.6 years; median AIDS-free time was estimated to be 11.6 years. CD4 cell loss was approximately linear when transformed to the square root scale as was the decline in CD4 percentage. Only HLA effects on slopes were found: A1,B8, DR3 was significantly associated with faster loss of both absolute CD4 cells and CD4 percentage (P < 0.001) and B27 was significantly associated with slower loss of CD4 percentage (P = 0.01). CONCLUSIONS: Edinburgh IDU do not seem to progress more rapidly than other cohorts with predominantly different risk activities. Older age was associated with poorer survival from AIDS but no gender effect was found for progression or overall survival. The clearest significant association with AIDS progression, mortality and loss of CD4 cells was the phenotype HLA A1,B8,DR3. In contrast HLA B27 was associated with slower loss of CD4 cells.

Cloning and expression in murine erythroleukemia cells: the soluble forms of the type I and type II tumor necrosis factor receptors fused to an immunogenic affinity tag.

We have cloned, expressed, and purified the extracellular domains of types I and II human tumor necrosis factor receptors. Both proteins were expressed in and secreted by murine erythroleukemia cells under the control of the human beta-globin promoter placed down-stream from the human globin locus control region. Secretion of both proteins was directed by the respective tumor necrosis factor receptor signal sequence. Each tumor necrosis factor receptor extracellular domain was expressed as a chimeric protein, fused to a carboxy terminal flexible peptide linker and an antigenic affinity tag. Secretion of both proteins into the growth medium in a hollow fiber bioreactor was achieved. A monoclonal antibody generated against the affinity tag allowed the purification of both proteins. These were isolated as biologically active products in that they bound human tumor necrosis factor-alpha in a 125I-radioiodinated ligand binding assay. The two proteins also bound tumor necrosis factor-alpha at approximately equimolar ratios as demonstrated by BIAcore sensorgram analysis.

Maternal factors in HIV transmission.

In order to identify features associated with an increased risk of transmission of HIV from seropositive women to their offspring, 70 children of 58 HIV seropositive mothers were studied. Fifty-six children were followed prospectively from pregnancy; in 14 identified after the puerperium, obstetric notes were reviewed and stored serum was tested. Twelve infants of 10 mothers were HIV infected. Risk of transmission was increased in the first year after seroconversion; 5/9 infants born at this time were infected compared with 7/61 born subsequently (P < 0.001). Progression to stage IV in transmitters was more likely, occurring in the mothers of 9 infected children at a median of 3 years (range 0.5-6.5) and in mothers of 19 non-infected children at a median of 5 years (range 1-7) (P = 0.032). Maternal CD4+ counts < 400 x 10(6)/l were found in 7/12 transmitting and 7/49 non-transmitting pregnancies (P < 0.01). Differences in HIV antigenaemia did not reach significance. These factors may influence the counselling of mothers regarding their child's and their own prognosis.

Use of zidovudine for drug misusers infected with human immunodeficiency virus.

The use of zidovudine in drug misusers, especially current drug misusers, has not been extensively studied. Since periods of abstinence may be interspersed with drug misuse, it is necessary to establish the safety of zidovudine in injection drug misuse-related human immunodeficiency virus (HIV) infection under a variety of conditions. HIV serology became available in October 1985 and we have now examined medically 289 HIV seropositive patients, 85% of whom acquired their infection via injection drug misuse. Since March 1987 we have treated 40 individuals with zidovudine, 25 of whom were former or current injection drug misusers and one who was a heterosexual contact of a drug misuser. Eighteen patients were taking various types of opiates. Six of this latter group injected either occasionally or regularly whilst taking zidovudine. There were no adverse clinical events associated with zidovudine treatment and continued opiate drug misuse whether by mouth or by injection. Although defaults from clinic visits were a problem, these defaults were not associated with any particular form of drug misuse. Compliance with zidovudine therapy as judged by change in the mean corpuscular volume was no different for the various risk groups. In our experience it is possible to treat safely current and former drug misusers with zidovudine.

Does infection with HIV affect the outcome of pregnancy?

PIP: Details are presented on the outcome of pregnancy in a group of Edinburgh women identified as positive for antibodies to HIV and in women who had a history of drug abuse or a partner known to be seropositive but who were themselves negative for HIV antibody. Pregnant women who had been tested for HIV up to June 1987 were identified. HIV state was known for 205 pregnant women. Most cases were determined during pregnancy, but in 23 (9 seropositive patients) it was determined retrospectively. Seropositivity was only found in women who had been intravenous drug users or whose partner was known seropositive. Of 50 women who were seropositive, 46 were intravenous drug users and 4 had seropositive partners. In 64 cases who were seronegative, 45 had used intravenous drugs since 1983, and 19 had a seropositive partner. These women tended to be young, unmarried, and smoked heavily. They usually lived in areas of Edinburgh with multiple deprivation. Both they and their partners were usually unemployed. In the seropositive group, spontaneous abortion showed an apparent increase, but this may be due to differences in ascertainment as the incidence in the seronegative group was low. Premature delivery, intrauterine growth retardation, and low birth weight were common compared with the total population, but seropositive and seronegative women did not differ from each other in these variables. Compared with rates in the total population of Edinburgh, the rates of prematurity and intrauterine growth retardation were increased more than 2-fold and the rate of low birthweight babies was increased nearly 4-fold, though the 1 twin pregnancy contributed to this. Adverse outcome was equally distributed between the seropositive and seronegative women, and there was no suggestion that infection with HIV itself had any effect. Although no evidence from this study shows that infection with HIV per se affects the outcome of pregnancy, none of these women showed symptomatic illness.^ieng