Anthony J. Pinching

Changing disease patterns in patients with AIDS in a referral centre in the United Kingdom: the changing face of AIDS.

OBJECTIVE--To study the changes in morbidity, mortality, and survival patterns in a population of patients with AIDS in the United Kingdom from 1982 to 1989. DESIGN--A retrospective analysis of inpatient and outpatient records of patients with AIDS. SUBJECTS--347 Patients with AIDS, predominantly homosexual or bisexual men. SETTING--Departments of immunology and genitourinary medicine, St Marys Hospital, London. MAIN OUTCOME MEASURES--Presenting diagnosis of AIDS, occurrence of other opportunist diseases, cause of death, and survival since AIDS was diagnosed, in particular for those patients with Pneumocystis carinii pneumonia or Kaposis sarcoma. RESULTS--The overall proportion of patients who developed P carinii pneumonia dropped from 56% (20/36) in 1984 to 24% (46/194) in 1989, although it has remained the index diagnosis in about half of new patients. Kaposis sarcoma has decreased as index diagnosis from 30% (20/67) to 20% (15/74) over the same period, though the prevalence has remained constant at around 35%. P carinii pneumonia accounted for 46% (16/35) of known causes of death in 1986 but only 3% (1/31) in 1989. Conversely, deaths due to Kaposis sarcoma rose from 14% (1/7) to 32% (10/31) between 1984 and 1989. Lymphoma accounted for an increased proportion of deaths among these patients with 16% (5/31) of deaths in 1989. Their median survival increased from 10 months in 1984-6 to 20 months in 1987. CONCLUSIONS--The changing patterns of disease in patients with AIDS have important implications both for health care provision and future medical research. Medical and nursing provision must be made for the increased morbidity of these diseases and the increased survival of these patients. Research should now be directed towards developing effective treatments for the opportunist infections which are currently more difficult to treat, the secondary malignancies of AIDS, as well as more effective immunorestorative treatments. Future changes in disease patterns must be recognised at an early stage so that resources can be adequately planned and allocated.

Alveolar macrophages in AIDS patients: increased spontaneous tumour necrosis factor-alpha production in Pneumocystis carinii pneumonia.

In order to assess the role of alveolar macrophages and their products in the control of Pneumocystis carinii pneumonia (PCP) and other infections in AIDS, bronchoalveolar lavage cells and peripheral blood mononuclear cells from HIV‐positive AIDS/ARC patients (with and without PCP) and HIV‐negative patients were counted and cultured in vitro; spontaneous and LPS‐induced tumour necrosis factor‐alpha (TNF‐α) production was measured. Markedly increased spontaneous TNF‐α production by alveolar macrophages and, to a lesser extent, peripheral blood monocytes was found in HIV‐positive patients with active PCP but not in patients without the infection. Higher TNF production was associated with lower counts of Pneumocystis in the bronchoalveolar lavage fluid. These results suggest that TNF‐α production by macrophages may play an important role in the control of Pn. carinii infection in AIDS.

Disseminated strongyloidiasis in AIDS: uncommon but important.

Disseminated Strongyloides stercoralis infection is a rare and severe but treatable complication of AIDS. We present a case where this infection was successfully treated and review the available literature. Cases may present many years after they have left an area endemic for Strongyloides infection, emphasizing the need for a full travel history. Symptoms are typically gastrointestinal and pulmonary, with infiltrates often seen on chest radiography. Diagnosis requires stool examination and biopsy of affected sites. Treatment with repeated courses of thiabendazole (25 mg/kg twice daily for 5 days) was successful in our case, but maintenance regimens have not yet been defined. The relative rarity of this complication of AIDS suggests that, where both infections are present, disseminated strongyloidiasis only arises either when HIV-induced immunodeficiency is profound or, possibly, when it is accompanied by impaired granulopoiesis.

Defective signal transduction—a common pathway for cellular dysfunction in HIV infection?

Qualitative defects in immune responsiveness after human immunodeficiency virus (HIV) infection have been well characterized and may play a key role in the development of HIV disease. However, no clear picture of the underlying mechanism of the functional deficiencies has yet emerged. In this article, Anthony Pinching and Keith Nye suggest that HIV or HIV proteins can sabotage transmembrane signalling and that this is of primary importance to the alterations in immune responsiveness.

Cytomegalovirus infection in AIDS. Patterns of disease, response to therapy and trends in survival

Among 347 AIDS patients seen at St Marys Hospital, London between 1983 and 1989, cytomegalovirus (CMV) disease was observed in 75 (22%). Of these, 58 (77%) had CMV retinitis, 26 (35%) CMV colitis, and 12 (16%) had CMV infection diagnosed at other sites. Relapse occurred in 71%. A favourable response to the use of ganciclovir as induction therapy for CMV retinitis was observed in 92%. Relapse of CMV retinitis occurred in 54% at a median time of 97 days. Neutropenia was the most frequent and serious side-effect of ganciclovir, 76% patients having neutrophil counts less than 1.0 x 10(9)/l and 48% less than 0.5 x 10(9)/l at some stage of therapy. Thrombocytopenia was also common, and platelet counts of less than 50 x 10(9)/l occurred in 43% patients on ganciclovir. The concurrent use of zidovudine made the development of severe neutropenia and thrombocytopenia more likely. Median survival following the diagnosis of CMV disease increased from 5-8 months between 1984 and 1987, to over 12 months in 1988. Patients with CMV colitis had a worse prognosis than patients with CMV retinitis, with median survival of 4.5 and 7 months respectively. In conclusion, CMV is an important opportunist infection in AIDS and both the disease and its treatment cause considerable morbidity. Hence, it is important to develop more effective and less toxic forms of therapy for CMV infection.

Kaposi's sarcoma in HIV infection treated with vincristine and bleomycin

ObjectiveTo evaluate the efficacy and toxicity of vincristine and bleomycin when used in combination to treat patients with progressive Kaposis sarcoma. DesignA retrospective case notes review. SettingThe departments of Immunology and Genito-Urinary Medicine, St Marys Hospital, London, UK. PatientsAll patients presenting with progressive Kaposis sarcoma and requiring chemotherapy between January 1987 and January 1990, who had received no previous systemic chemotherapy. InterventionsTreatment with vincristine (2 mg) and bleomycin (30 mg, 18 h infusion), or vinblastine (2.5–5.0 mg) if peripheral neuropathy developed. Treatment with zidovudine and prophylaxis of opportunistic infections where indicated. Outcome measuresResponse, toxicity and survival. ResultsOverall, patients had a poor prognosis: 33 out of 46 (72%) had had a previous opportunistic infection, had a mean CD4 count of 144 x 106 (20 out of 46 tested) and a mean Karnofsky index of 75.4. They received a median of five cycles of therapy: a partial response was achieved in twenty-six patients (57%), disease progression was halted in a further 16 (35%), while disease progression continued in four (9%) despite therapy; there were no complete responders. Mean duration of response was 2 months (s.d., 1.26 months), survival was 8 months (s.d., 6.7 months) from start of therapy and 17 months (s.d., 8.9 months) from first AIDS diagnosis. On multivariate analysis the best predictor of mortality was the presence of previous opportunistic infection (P = 0.00653). Side-effects were minimal in comparison with other studies. The most common side-effect, in 13 cases (28%), was peripheral neuropathy, which may in part represent the prevalence of HIV neuropathy or remain as background. Haematological toxicity was uncommon. ConclusionsTreatment for HIV-related Kaposis sarcoma in advanced HIV disease is becoming more necessary as disease profiles change. Conventional chemotherapy regimens for malignancy are not well tolerated in these patients and may not be indicated. This regimen is effective and has low toxicity in AIDS patients. Non-responders should be considered for more intensive regimens.

Changing use of hospital services and costs at a London AIDS referral centre, 1983-1989

Objective.To describe the use of hospilal-based services and associated costs over time for HIV-infected individuals by disease stage and year of treatment. Methods: Data on service use were abstracted from inpalient and outpatient case-notes of 459 HIV-infected patients (121 asymptomatic and 338 AIDS patients) treated at St Marys Hospital, London between 1983 and 1989. Cost estimates were derived from a survey of the 37 departments involved with HIV-related care. The number and type of admissions and outpatient visits, referral and discharge venues, number and type of tests and procedures performed, drugs prescribed and associated costs for the study period were the outcome measures used. Results.Most patients were homosexual men. At the time of first HIV-rclated visit, 80.7% lived in London. Most day cases and planned admissions were organized through the outpatient clinic; 31% of emergency admissions were initiated by patients themselves. For people with AIDS the number of day case admissions increased while planned admissions decreased. There was a marked reduction in the duration of inpatient stays, especially for AIDS patients. Costs associated with inpatient care decreased concomitantly. The number of outpatient visits for patients with symptomatic disease increased, resulting in increased outpatient expenditure. Asymptomatic patients had fewer inpatient tests, while outpatient tests did not change over time; costs followed similar patterns. Mean inpatient and outpatient drug-days prescribed did not change nor did average inpatient drug-costs although outpatient drug-costs increased. Inpatient tests performed on symptomatic non-AIDS patients decreased, while mean outpatient tests increased; average costs followed similar patterns. Inpatient drug-days prescribed and costs remained the same, while outpatient drug-days and average drug-costs increased during the study period. For AIDS patients, the number of inpatient tests performed and their average costs decreased but outpatient tests performed increased, though their average costs remained the same. Mean inpatient drug-days prescribed and average drug-costs decreased, while number of outpatient drug-days prescribed and average drug-costs increased markedly over time. For each disease category, expenditure on admissions and related tests decreased over time, while expenditure on outpatient visits and drug-costs increased. Conclusions.The shift from an inpatient- to an outpatient-based service has resulted in fewer patients being investigated and treated in hospital and more as outpatients. This has resulted in a reduction of inpatient-related costs, while outpatient-related costs have increased. The overall contribution of drug-costs to the total cost has increased greatly over time. With the anticipated advent of new antiviral compounds, the importance of ascertaining their effectiveness as well as their efficacy will become crucial.

Technical influences on immunophenotyping by flow cytometry The effect of time and temperature of storage on the viability of lymphocyte subsets

The typing of lymphocyte subsets may be influenced by a variety of technical influences including the duration and temperature of sample storage and the method used for staining samples. We have extended a previous study examining the effect of storage conditions on the baseline values of a number of lymphocyte subsets. EDTA-anticoagulated samples from 13 HIV-1-positive and 15 healthy laboratory controls were analyzed for a number of lymphocyte subsets (CD3+, CD4+/CD3+, and CD8+/CD3+ T cells and CD19+ B cells) (whole blood lysis method, Becton-Dickinson FACScan flow cytometer and reagents) at 0, 24, 48, 72, and 96 h after storage at 4 degrees C, 17 degrees C or 21 degrees C. During storage at both 4 degrees C and 21 degrees C, there were significant changes in baseline values of the majority of lymphocyte subsets and some of these were related to the HIV status of the donor. The optimum temperature for storage in our system appeared to be around 17 degrees C in both our study groups. We have also used propidium iodide in order to discriminate between viable and non-viable cells during flow cytometry of lymphocytes from eight HIV-1-positive and five control subjects. The results show that for both HIV-positive and control samples stored at 4 degrees C, and for control subjects at 21 degrees C, the changes in baseline values of lymphocyte subsets observed were not due to selective loss of particular subsets arising from cell death during storage. However, there was substantial loss of cells from all three subsets in HIV-positive subjects during storage at 21 degrees C, with loss of CD8+ and CD3+ T cells being more significant than loss of CD4+ T cells.

AIDS and HTLV-III/LAV infection: consequences for obstetrics and perinatal medicine

Summary. This paper was prepared at the request of the Scientific Advisory Committee of the Royal College of Obstetricians and Gynaecologists It includes data distilled from many published and unpublished reports, including those presented at the International Conference on AIDS held in Atlanta, Georgia in April 1985. The urgency of the issues raised would seem to merit including all available data in this way.

Increase in dendritic cell numbers, their function and the proportion uninfected during AZT therapy

The effects of AZT treatment on the numbers, level of infection and function of peripheral blood dendritic cells (DC) were examined in patients with HIV infection. This was a cross‐sectional study of patients before AZT treatment and up to 20 months after initiation of treatment. Numbers of DC separated by density gradients were below the normal range in patients before treatment, but increased between 3 and 12 months of treatment. The numbers of DC per provirus copy rose from around 100 cells to 5000 cells and this decrease in viral load in DC was significant between 3 and 20 months of treatment. The capacity of DC to stimulate allogeneic T cell proliferation was low before treatment and significantly higher between 6 and 12 months after the start of AZT. This study indicated that AZT treatment produced beneficial effects on DC by increasing their numbers, reducing the provirus load and increasing their function in stimulating T cells. These results support the thesis that the function of these potent antigen‐presenting cells is important in development of immunological defects in AIDS, and that effects of AZT treatment on DC may provide a measure of its therapeutic effect.