Length of survival of patients with acquired immune deficiency syndrome in the United Kingdom.

An analysis of the lengths of survival of patients with the acquired immune deficiency syndrome presenting with different opportunistic diseases was performed using epidemiological data routinely collected at the PHLS Communicable Disease Surveillance Centre. The overall crude case fatality rate was 55.4% (93/168). The median survival times were: 21.2 months for Kaposi''s sarcoma, 12.5 months for Pneumocystis carinii pneumonia, and 13.3 months for other opportunistic infections. The shortest median survival time (6.6 months) was found for those with both Kaposi''s sarcoma and P carinii pneumonia. There were significant differences between durations of survival of patients with Kaposi''s sarcoma and those with all other diseases, which indicated impaired cellular immunity apart from opportunistic infections. This analysis shows that those with Kaposi''s sarcoma alone have the most favourable prognosis.     

Is risk of Kaposi's sarcoma in AIDS patients in Britain increased if sexual partners came from United States or Africa?

OBJECTIVE--To determine whether the risk of Kaposi''s sarcoma in patients with AIDS is increased by sexual contact with groups from abroad with a high incidence of Kaposi''s sarcoma. DESIGN--Analysis of risk of Kaposi''s sarcoma in patients with AIDS, according to country of origin of their sexual partners. SETTING--United Kingdom. PATIENTS--2830 patients with AIDS reported to the Communicable Disease Surveillance Centre and the Communicable Disease (Scotland) Unit up to March 1990, of whom 566 had Kaposi''s sarcoma. MAIN OUTCOME MEASURES--Percentage of patients with AIDS who had Kaposi''s sarcoma. RESULTS--537 of 2291 homosexual or bisexual men (23%) with AIDS had Kaposi''s sarcoma; 10% (14/135) of the men and women who acquired HIV by heterosexual contact had Kaposi''s sarcoma. None of the 316 subjects who acquired HIV through non-sexual routes had Kaposi''s sarcoma. Kaposi''s sarcoma was more common among homosexual men whose likely source of infection included the United States (171/551, 31%) or Africa (9/34, 26%) than among those infected in the United Kingdom (119/625, 19%) (p less than 0.05). CONCLUSION--The data suggest that Kaposi''s sarcoma is caused by a sexually transmissible agent which was introduced into the British homosexual population mainly from the United States [corrected].     

Surveillance of AIDS in the United Kingdom.

The surveillance of cases of the acquired immune deficiency syndrome (AIDS) in the United Kingdom is described and a preliminary analysis made of the 1012 cases that were reported to the end of August 1987. Homosexuals were the largest risk group. For the first time it is possible to present cases by the date of diagnosis and by the regional health authority of residence. The rate of increase of new cases shows no sign of slowing down. One third of patients with AIDS lived in a different regional health authority from that in which their disease had been diagnosed. The geographical distribution varied with the risk group. The commonest presenting clinical feature at diagnosis was Pneumocystis carinii pneumonia. Kaposi''s sarcoma was considerably more common among homosexuals than among people in other groups at risk.     

Infectious syphilis in Canada in 1986.

Thirteen men with a median age of 37 (range 28 to 46) years who had extensive Kaposi''s sarcoma associated with acquired immune deficiency syndrome (AIDS) were treated with combination chemotherapy and alpha-interferon. Four patients had stage III disease and nine had stage IV disease (one with pulmonary and eight with gastrointestinal involvement). Treatment consisted of monthly courses of actinomycin D, 1 mg/m2, and vinblastine sulfate, 6 mg/m2, given intravenously on day 1, bleomycin, 10 mg/m2 given intravenously on days 1 and 8, and human lymphoblastoid (alpha-) interferon, 10 million U/m2 given subcutaneously three times a week for six doses starting on day 14. Forty-one treatment cycles (median 3, range 1 to 12) were administered. The median granulocyte and platelet counts on day 14 before the start of interferon therapy were 600 X 10(9)/L and 134 X 10(9)/L respectively; the counts did not fall further during interferon therapy. There was no difference in T-cell subsets, 2'',5''-oligoadenylate synthetase level or results of blastogenesis studies after interferon therapy. Four patients required admission to hospital for neutropenia-associated fever. A complete response (of 24 weeks'' duration) was seen in one patient and a partial response (of 14 to 44 weeks'' duration) in four. One patient had a mixed response, with regression of skin involvement but progression of pulmonary disease. The median length of survival was 48 (range 4 to 143) weeks. Eleven patients died of progressive Kaposi''s sarcoma, one of lymphoma and one of Pneumocystis carinii pneumonia. The results suggest that this form of therapy is not appropriate for patients with Kaposi''s sarcoma associated with AIDS.     

Serum lactic dehydrogenase predicts mortality in patients with AIDS and Pneumocystis pneumonia.

Serum lactic dehydrogenase (LDH) activity was compared with mortality in patients with the acquired immunodeficiency syndrome (AIDS) and Pneumocystis carinii pneumonia during the first four days of admission to assess the test''s predictive value. In 30 admissions, 29 patients who survived an episode of Pneumocystis pneumonia had a mean LDH value of 385 IU, with five values greater than 520 IU. Eight with pneumonia who died had a mean value of 926 IU: all had values higher than 520 IU. The mean LDH values for 20 patients with AIDS (35 admissions) who survived and 4 who died of non-Pneumocystis disease were 240 IU and 350 IU, respectively; these patients were the control population. The positive and negative predictive values for survival using 520 IU as the threshold are 61% and 100%. Thus, LDH measurements in the first days of admission for P carinii pneumonia predict mortality and are useful in guiding future management.     

Survival after diagnosis of AIDS: a prospective observational study of 2625 patients. Royal Free/Chelsea and Westminster Hospitals Collaborative Group.

OBJECTIVE: To estimate median survival and changes in survival in patients diagnosed as having AIDS. DESIGN: Prospective observational study. SETTING: Clinics in two large London hospitals. SUBJECTS: 2625 patients with AIDS seen between 1982 and July 1995. MAIN OUTCOME MEASURES: Survival, estimated using lifetable analyses, and factors associated with survival, identified from Cox proportional hazards models. RESULTS: Median survival (20 months) was longer than previous estimates. The CD4 lymphocyte count at or before initial AIDS defining illness decreased significantly over time from 90 x 10(6)/1 during 1987 or earlier to 40 x 10(6)/1 during 1994 and 1995 (P < 0.0001). In the first three months after diagnosis, patients in whom AIDS was diagnosed after 1987 had a much lower risk of death (relative risk 0.44, 95% confidence interval 0.22 to 0.86; P = 0.017) than patients diagnosed before 1987. When the diagnosis was based on oesophageal candidiasis or Kaposi''s sarcoma, patients had a lower risk of death than when the diagnosis was based on Pneumocystis carinii pneumonia (0.21 (0.07 to 0.59). P = 0.0030 and 0.37 (0.16 to 0.83), P = 0.016). Three months after AIDS diagnosis, the risk of death was similar in patients whose diagnosis was made after and before 1987 (1.02 (0.79 to 1.31), P = 0.91). There were no differences in survival between patients diagnosed during 1988-90, 1991-3, or 1994-5. CONCLUSIONS: In later years, patients were much more likely to survive their initial illness, but long term survival has remained poor. The decrease in CD4 lymphocyte count at AIDS diagnosis indicates that patients are being diagnosed as having AIDS at ever more advanced stages of immunodeficiency.     

Survival differences in European patients with AIDS, 1979-89. The AIDS in Europe Study Group.

OBJECTIVES--To examine the pattern of survival and factors associated with the outcome of disease in patients with AIDS. DESIGN--Inception cohort. Data collected retrospectively from patients'' charts. SETTING--52 clinical centres in 17 European countries. SUBJECTS--6578 adults diagnosed with AIDS from 1 January 1979 to 31 December 1989. MAIN OUTCOME MEASURES--Survival after the time of diagnosis. RESULTS--The median survival after diagnosis was 17 months, with an estimated survival at three years of 16% (95% confidence interval 15% to 17%). Patients diagnosed in southern Europe had a shorter survival, particularly immediately after the time of diagnosis, compared with patients diagnosed in central and northern Europe (survival at one year (95% confidence interval) 54% (52% to 56%) 66% (64% to 68%), 65% (63% to 66%), respectively. The three year survival, however, was similar for all regions. The regional differences in survival were less pronounced for patients diagnosed in 1989 compared with earlier years. Improved survival in recent years was observed for patients with a variety of manifestations used to define AIDS but was significant only for patients diagnosed with Pneumocystis carinii pneumonia. The three year survival, however, remains unchanged over time. CONCLUSIONS--Survival of AIDS patients seems to vary within Europe, being shorter in southern than central and northern Europe. The magnitude of these differences, however, has declined gradually over time. Short term survival has improved in recent years, but the long term prognosis has remained equally poor, reflecting the fact that the underlying infection with HIV and many of the complicating diseases remains essentially uncontrolled.     

Severe acquired immunodeficiency in European homosexual men.

Four previously healthy Danish homosexual men developed Kaposi''s sarcoma or opportunistic infections with fever of unknown origin and lymphadenopathy. One patient died of a Pneumocystis carinii pneumonia. Three patients had defective cell-mediated immunity with absent leucocyte interferon production and decreased proliferative response to mitogens and antigens. T lymphocyte helper subsets and natural killer cell activity were reduced. Unstimulated mononuclear cells produced leucocyte migration inhibitor factor. Two patients were sexual partners and three had never been to the USA, where cases of severe acquired immunodeficiency have been reported. Thus, the syndrome must also be suspected in European homosexual men who present with fever of unknown origin, opportunistic infections, or Kaposi''s sarcoma.     

Use of CD4 lymphocyte count to predict long-term survival free of AIDS after HIV infection.

OBJECTIVE--To estimate the probability of remaining free of AIDS for up to 25 years after infection with HIV by extrapolation of changes in CD4 lymphocyte count. DESIGN--Cohort study of subjects followed from time of HIV seroconversion until 1 January 1993. Creation of model by using extrapolated linear regression slopes of CD4 count to predict development of AIDS after 1993. SETTING--Regional haemophilia centre in teaching hospital. SUBJECTS--111 men with haemophilia infected with HIV during 1979-85. Median length of follow up 10.1 years, median number of CD4 counts 17. The model was not fitted for three men because only one CD4 measurement was available. MAIN OUTCOME MEASURES--Development of AIDS. INTERVENTIONS--From 1989 prophylaxis against candida and Pneumocystis carinii pneumonia and antiretroviral drugs when CD4 count fell below 200 x 10(6)/l. RESULTS--44 men developed AIDS up to 1 January 1993. When AIDS was defined as a CD4 count of 50 x 10(6)/l the model predicted that 25% (95% confidence interval 16% to 34%) would survive for 20 years after seroconversion and 18% (11% to 25%) for 25 years. Changing the CD4 count at which AIDS was assumed to occur did not alter the results. Younger patients had a higher chance of 20 year survival than older patients (32% (12% to 52%) for those aged < 15, 26% (14% to 38%) for those aged 15-29, and 15% (0% to 31%) for those aged > or = 30). CONCLUSIONS--These results suggest that even with currently available treatment up to a quarter of patients with HIV infection will survive for 20 years after seroconversion without developing AIDS.     

AIDS: acquired immunodeficiency syndrome.

Acquired immunodeficiency syndrome, or AIDS, is a new illness that occurs in previously healthy individuals. It is characterized by immunodeficiency, opportunistic infections and unusual malignant diseases. Life-threatening single or multiple infections with viruses, mycobacteria, fungi or protozoa are common. A rare neoplasm, Kaposi''s sarcoma, has developed in approximately one third of patients with AIDS. More than 800 cases of AIDS have been reported in North America, over 24 of them in Canada. The majority of patients are male homosexuals, although AIDS has also developed in abusers of intravenously administered drugs, Haitian immigrants, individuals with hemophilia, recipients of blood transfusions, prostitutes, and infants, spouses and partners of patients with AIDS. The cause of AIDS is unknown, but the features are consistent with an infectious process. Early diagnosis can be difficult owing to the nonspecific symptoms and signs of the infections and malignant diseases. Therefore, vigilance by physicians is of utmost importance.     

AIDS in Haitian immigrants and in a Caucasian woman closely associated with Haitians.

In Montreal the acquired immune deficiency syndrome (AIDS) was seen in eight Haitian immigrants and one Caucasian woman who had lived with Haitian immigrants for 3 years before the onset of her illness. AIDS was characterized by opportunistic infections alone in seven patients, by opportunistic infection and Kaposi''s sarcoma in one patient and by chronic generalized lymphadenopathy in one patient. Five of the patients had presented with Mycobacterium tuberculosis infections 1 to 12 months before the onset of opportunistic infections. All nine patients were found to have recall anergy by skin testing for delayed hypersensitivity. Enumeration of the lymphocyte subpopulations in three patients showed a marked inversion of the ratio of helper to suppressor T lymphocytes. Six of the patients died as a result of the opportunistic infections; autopsies showed no recognizable causes of immunodeficiency. Thus, there is in Montreal a third clustering of AIDS cases in North America related to Haitian immigrants.     

Detection of Pneumocystis carinii in serum of AIDS patients with Pneumocystis pneumonia by the polymerase chain reaction.

Amplification of DNA by the polymerase chain reaction (PCR) offers a highly sensitive and specific method for detecting DNA sequences in biological samples. We applied this technology to develop an assay for the P. carinii dihydrofolate reductase (DHFR) gene. This assay was found to be sensitive enough to detect as little as 1 organism-'equivalent' of DHFR DNA. In rats with experimentally-induced P. carinii pneumonia, DHFR DNA amplification demonstrated the presence of pulmonary P. carinii 2 wk prior to the onset of histopathological changes. When rat serum was analyzed by PCR, serum P. carinii DNA was found in 5 of 14 experimental rats. Finally, P. carinii DNA was detected in the serum of 7 of 18 patients (39%) with AIDS and active P. carinii pneumonia. These results suggest that circulating serum P. carinii DNA can be detected frequently in the course of pulmonary infection and may represent a blood-borne phase of infection. The PCR detection of P. carinii DNA provides a useful tool to study the natural history of P. carinii infection and may offer a non-invasive diagnostic procedure in some patients with P. carinii pneumonia.     

AIDS: acquired immunodeficiency syndrome

Acquired immunodeficiency syndrome, or AIDS, is a new illness that occurs in previously healthy individuals. It is characterized by immunodeficiency, opportunistic infections and unusual malignant diseases. Life-threatening single or multiple infections with viruses, mycobacteria, fungi or protozoa are common. A rare neoplasm, Kaposi''s sarcoma, has developed in approximately one third of patients with AIDS. More than 800 cases of AIDS have been reported in North America, over 24 of them in Canada. The majority of patients are male homosexuals, although AIDS has also developed in abusers of intravenously administered drugs, Haitian immigrants, individuals with hemophilia, recipients of blood transfusions, prostitutes, and infants, spouses and partners of patients with AIDS. The cause of AIDS is unknown, but the features are consistent with an infectious process. Early diagnosis can be difficult owing to the nonspecific symptoms and signs of the infections and malignant diseases. Therefore, vigilance by physicians is of the utmost importance.     

Pathogens in children with severe combined immune deficiency disease or AIDS.

We evaluated the frequency and severity of illnesses caused by various microbial pathogens in 15 children with severe combined immune deficiency disease (SCID) and 8 with acquired immune deficiency syndrome (AIDS). There were 35 viral, 23 bacterial, 19 mycotic and 13 parasitic infections. Nineteen of the 23 patients died of infection; Pneumocystis carinii pneumonia, giant-cell pneumonia due to paramyxoviruses and various disseminated viral infections were responsible for most deaths in both groups. The emerging role of paramyxoviruses was illustrated by the fact that they were responsible for giant-cell pneumonia in seven patients. Viral enteric infections were frequent in both groups. The variety of infectious microorganisms and the severity of resulting illnesses in the patients with AIDS were similar to those in the patients with SCID.     

Pneumocystis carinii pneumonia and AIDS

An infection with Pneumocystis carinii with clinical symptoms of pneumonia is particularly frequent in patients with AIDS. The authors discuss current knowledge on Pneumocystis carinii pneumonia, including clinical course, possibility of diagnosis, and chemotherapy in patients with AIDS.     

Clinical and bronchoscopic diagnosis of suspected pneumonia related to AIDS.

In a series of 25 patients with suspected pneumonia related to the acquired immune deficiency syndrome (AIDS) the first 12 underwent routine fibreoptic bronchoscopy and bronchoalveolar lavage with or without transbronchial biopsy before treatment. Eight were found to have Pneumocystis carinii pneumonia and had typical clinical presentations with a prolonged history of symptoms, including a dry cough, and bilateral diffuse alveolar or interstitial shadowing in chest radiographs. Among the subsequent 13 cases, 11 had similar clinical presentations and were treated with high doses of intravenous co-trimoxazole without bronchoscopy first. Bronchoscopy was performed in those who deteriorated at any stage or failed to improve by the fifth day of treatment. Nine patients recovered and were discharged. In two patients who died P carinii pneumonia was confirmed in one but no diagnosis was made in the other. The early and late survival in both groups of patients was similar. In patients at high risk for AIDS who have clinical features suggestive of P carinii pneumonia starting treatment with intravenous co-trimoxazole is justified. The few patients who deteriorate or fail to respond should undergo bronchoscopy with bronchoalveolar lavage and transbronchial biopsy.     

Dynamics of Pneumocystis carinii-Specific Immune Complexes in AIDS Patients with P. carinii Pneumonia

Pneumocystis carinii-specitic immune complexes were detected by immunoblot and enzyme-linked immunosorbent assay (ELISA) in 53% of sera from Acquired Immunodeficiency Syndrome (AIDS) patients with P. carinii pneumonia (PCP). Resolution of glycoprotein antigenemia (50–55 kd = dominant species) appears to correlate with successful PCP drug therapy and recovery. An epitope map has been constructed from im-munoblots of P. carinii hydrolysates and from human and murine scrum containing P. carinii antigens.     

Upper gastrointestinal Kaposi's sarcoma in patients positive for HIV antibody without cutaneous disease

Six patients with antibodies to the human immunodeficiency virus (HIV) and with persistent gastrointestinal symptoms of HIV infection but without cutaneous lesions of Kaposi''s sarcoma underwent endoscopy. Four also underwent barium meal examination. In all six cases small lesions were seen in the stomach at endoscopy, and histological examination of biopsy specimens taken from the lesions confirmed the diagnosis of Kaposi''s sarcoma. The barium meal examinations were reported as normal in three patients and showed oesophageal candidiasis in the fourth.These findings suggest that Kaposi''s sarcoma of the upper gastrointestinal tract is common in patients positive for HIV antibody, even those without cutaneous lesions. Endoscopy, with biopsy of suspicious lesions, is necessary to make the diagnosis and is recommended in all HIV antibody positive patients with persistent upper gastrointestinal symptoms.     

MicroRNAs control herpesviral dormancy

Infections by herpesviruses are widespread in humans, and are the causes for several important diseases. Gammaherpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV) is etiologically associated with Kaposi's sarcoma (KS), a highly inflammatory and angiogenic cancer commonly found in AIDS patients.1 KSHV is also associated with primary effusion lymphoma and a subset of multicentric Castleman’s disease, two rare lymphoproliferative malignancies.     

Dynamics of Pneumocystis carinii-specific immune complexes in AIDS patients with P. carinii pneumonia

Pneumocystis carinii-specific immune complexes were detected by immunoblot and enzyme-linked immunosorbent assay (ELISA) in 53% of sera from Acquired Immunodeficiency Syndrome (AIDS) patients with P. carinii pneumonia (PCP). Resolution of glycoprotein antigenemia (50-55 kd = dominant species) appears to correlate with successful PCP drug therapy and recovery. An epitope map has been constructed from immunoblots of P. carinii hydrolysates and from human and murine serum containing P. carinii antigens.