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Biomedical subjects

A N Phillips

Publications and source records attributed to A N Phillips.

At least 145 records · Page 8Linked to original sources
PubMed1995

Changes in survival over time after a first episode of Pneumocystis carinii pneumonia for European patients with acquired immunodeficiency syndrome. Multicentre Study Group on AIDS in Europe.

BACKGROUND: Factors associated with improved survival over time for patients with the acquired immunodeficiency syndrome (AIDS) who have Pneumocystis carinii pneumonia at diagnosis are not clearly defined. METHODS: An inception cohort of 2533 patients with AIDS, diagnosed from 1979 to 1989, from 52 centers in 17 European countries was studied. Survival 3 months and 3 years after diagnosis was estimated by Kaplan-Meier life tables. Independent predictors of survival were analyzed by construction of Cox proportional hazards models. RESULTS: Patients in whom AIDS and P carinii pneumonia had been diagnosed before 1988 had a poorer 3-month (ie, short-term) survival, whereas the survival 1 and 2 years after P carinii pneumonia was lower only for patients whose disease was diagnosed before 1987 compared with those with more recent diagnoses. Other variables associated with poorer outcome were greater age, infection via blood transfusion, diagnosis made in south Europe, and coexisting illnesses. After controlling for these prognostic markers in multivariate analysis, improvement in survival over time was still evident. For patients who survived the P carinii pneumonia episode, both zidovudine and secondary prophylaxis for P carinii pneumonia initiated around the time of diagnosis were associated with improved survival, and, after controlling for these treatment variables, no statistically significant improvement in survival over time was observed. CONCLUSIONS: Survival after an episode of P carinii pneumonia has improved within recent years. Increased awareness of early symptoms of P carinii pneumonia and better treatment of the pneumonia may have led to improvement in short-term survival over time, whereas the introduction of zidovudine and increased use of secondary P carinii pneumonia prophylaxis may have resulted in the recent increase in survival 1 and 2 years after the diagnosis. However, 3-year survival remained unchanged over time, implying that the underlying human immunodeficiency virus infection and other complications are not effectively controlled.

AIDS-Related Opportunistic Infections↗
PubMed1995

Markers of immune cell activation and disease progression. Cell activation in HIV disease.

Immune cell activation is a feature of infection with the human immunodeficiency virus (HIV). Here we report our studies on a cohort of over 400 patients with HIV infection studied cross-sectionally and longitudinally to examine the relationship between markers of immune cell activation and disease progression. To examine disease progression, 340 patients with HIV infection but without AIDS were followed for a total of 574 patient years, during which 56 developed AIDS. In our first study, 157 patients in CDC groups II-IV were examined cross-sectionally for in vivo expression of the activation markers HLA-DR and CD25 on CD3, CD4 and CD8 T cells. Levels of CD3+ HLA-DR+ T cells are high in HIV infection and show a significant negative correlation with CD4 counts (r = 0.52; p < 0.001). The appearance of HLA-DR+ CD3+ T cells is an early feature of asymptomatic HIV+ patients, with a greater proportion (82%) showing abnormally high levels of these than abnormally low levels of CD4 (52%; p < 0.001). Examining activation of the CD4 subset specifically is likely to be of greater interest, given that this cell is the viral target. Indeed, we found that in the cross-sectional study, levels of HLA-DR+ and CD25+ CD4 lymphocytes show a step-wise linear increase with increasing disease severity (significant test for linear trend; p < 0.001). In our previous studies, only declining CD4 count has shown such a significant linear trend. These data suggest that measuring activated CD4+ T cells in the periphery may be a powerful predictive tool. In our second study, we examined the expression of other markers acquired (CD45R0) and lost (CD45RA) following activation of naïve T cells. Examining expression of these on CD4 and CD8 cells cross-sectionally in 71 HIV+ patients, we found abnormalities in percentage levels of CD45RA+ and CD45R0+ populations, none of which showed any relationship to disease severity. Intriguingly, however, we noted that the surface density of both CD45RA and CD45R0 molecules on CD4 and CD8 cells was markedly and significantly reduced at all stages of HIV infection (eg relative specific fluorescence reduced by up to 50%; p < 0.001). This abnormality was confirmed in studies using antibodies to a common epitope on all CD45 isoforms (pan-CD45) and to the CD45RB isoform. Finally, returning to the question of immune cell markers of activation and disease progression, we have examined some of the best documented markers in our longitudinal study.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1995

The effect of CMV infection on progression of human immunodeficiency virus disease is a cohort of haemophilic men followed for up to 13 years from seroconversion.

The effect of prior infection with cytomegalovirus (CMV) on progression of HIV disease in a cohort of 111 men with haemophilia was studied after 13 years follow-up. The relative hazards associated with CMV positivity on progression to AIDS, death and a CD4 count of 0.05 x 10(9)/l were 2.28, 2.42 and 2.34, respectively. CMV seropositive patients were significantly older than the seronegative and this was controlled for by using a Cox proportional hazards model. The relative hazards for the three endpoints decreased to 1.89, 1.82 and 1.93 respectively and were marginally non-significant (P = 0.05, 0.08 and 0.08 for the three endpoints respectively). We conclude that this cohort continues to show evidence of a 'co-factor' effect associated with prior infection with CMV which is confounded by age but not completely explained by age differences. The potential biological significance of these results is discussed in the context of recent controlled clinical trials which show a survival benefit from long-term high-dose acyclovir, a drug with activity in vivo against CMV and other herpesviruses.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Factors associated with the development of Pneumocystis carinii pneumonia in 5,025 European patients with AIDS. AIDS in Europe Study Group.

This study examined the factors associated with the development of a first episode of Pneumocystis carinii pneumonia (PCP) in 5,025 patients with AIDS, including 1,976 patients with primary PCP at the time of AIDS diagnosis and 635 with primary PCP occurring subsequently. Compared with untreated patients, patients treated with zidovudine were at similar risk of developing PCP during the first year of therapy but were at greater risk after longer intervals of treatment. The following factors were associated with an increased risk of PCP (either at the time of AIDS diagnosis or thereafter): lack of primary PCP prophylaxis, male homosexuality/bisexuality, diagnosis of AIDS in northern Europe, and CD4 cell count below 200 x 10(6)/L at the time of AIDS diagnosis. Patients with severe weight loss had a 60% higher risk of developing PCP during follow-up than those without such weight loss. Thus, the occurrence of PCP depended on geographic location, mode of acquisition of human immunodeficiency virus and AIDS, degree of immunodeficiency, and use of various treatment regimens.

AIDS-Related Opportunistic Infections↗
PubMed1995

Coinfection of hepatitis C virus with human immunodeficiency virus and progression to AIDS. Italian Seroconversion Study.

To assess the influence of hepatitis C virus (HCV) on the natural history of human immunodeficiency virus (HIV) infection, a longitudinal study was conducted among 416 HIV-positive, AIDS-free persons infected through injecting drug use or homosexual or heterosexual activity and with known seroconversion dates. End points were diagnosis of AIDS and a CD4 cell count of < 100 x 10(6) cells/L. HCV antibodies were detected in 214 persons (51.4%). The crude relative hazard (RH) of progression to AIDS was 0.96 (95% confidence interval [CI], 0.53-1.76) for HCV-coinfected participants compared with those not coinfected. After adjustment for CD4 cell count, the RH was 0.97 (95% CI, 0.52-1.79). Similar RHs were found using a CD4 cell count of < 100 x 10(6) cells/L as the end point. The median CD4 cell loss was 4.83 x 10(6) cells/L per month among coinfected persons and 5.70 x 10(6) cells/L per month among the others. These results suggest that coinfection with HCV does not influence clinical and immunologic progression of HIV disease.

Acquired Immunodeficiency Syndrome↗
PubMed1994

HIV disease progression in 854 women and men infected through injecting drug use and heterosexual sex and followed for up to nine years from seroconversion. Italian Seroconversion Study.

OBJECTIVE: To compare the progression of HIV-1 infection in men and women followed up for up to nine years after an accurately estimated date of seroconversion. DESIGN: Prospective observational study. SETTING: 16 HIV outpatient clinics across Italy. SUBJECTS: 321 women and 533 men infected with HIV through injecting drug use or heterosexual sex and with accurately estimated dates of seroconversion. MAIN OUTCOME MEASURES: Progression to severe CD4 lymphocytopenia (CD4 lymphocyte count < 200 x 10(6)/l), development of AIDS defining diseases, and death from AIDS. RESULTS: Thirty two women and 67 men developed AIDS at Kaplan-Meier progression rates of 25% (95% confidence interval 13.8% to 35.5%) and 23% (15.6% to 30.4%), respectively, 7 years after seroconversion. In a Cox proportional hazards model the relative hazard was 0.93 (that is, a slightly lower hazard in women) before and 1.10 (0.70 to 1.72) after adjusting for age, HIV exposure group, and year of seroconversion. When CD4 lymphocytopenia and death from AIDS were used as end points the results were similar, with adjusted relative hazards of 0.95 (0.63 to 1.42) and 0.72 (0.48 to 1.79) respectively. In both women and men the risk of developing AIDS before the CD4 lymphocyte count had declined below 200 x 10(6)/l was small (3% in women, 6% in men). The estimated median count at which AIDS developed in women (34 x 10(6)/l; 10 x 10(6) to 44 x 10(6)) was similar to that for men (44 x 10(6)/l; 22 x 10(6) to 60 x 10(6)). CONCLUSION: There seems to be little evidence for appreciable differences in the natural course of HIV infection between men and women followed up from the time of seroconversion.

Acquired Immunodeficiency Syndrome↗
PubMed1994

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.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Comparison of long-term prognosis of patients with AIDS treated and not treated with zidovudine. AIDS in Europe Study Group.

OBJECTIVE: To determine the association between elapsed time since starting zidovudine and survival in patients with acquired immunodeficiency syndrome (AIDS). DESIGN: Inception cohort and observational study of patients treated and not treated with zidovudine. SETTING: Fifty-one centers in 17 European countries. PATIENTS: A total of 4484 patients diagnosed as having AIDS from 1979 to 1989 who survived their initial AIDS-defining event and who had not started zidovudine before AIDS diagnosis. MAIN OUTCOME MEASURES: Use of zidovudine and mortality. RESULTS: Among patients who did not receive zidovudine, the death rate was approximately constant for the first 5 years after AIDS diagnosis. For patients treated with zidovudine, the death rate within the first year since starting zidovudine was markedly lower than for untreated patients who had developed AIDS at the same time (relative rate, 0.47; 95% confidence interval [CI], 0.42 to 0.51). For longer times since starting zidovudine, the association with reduced mortality rate was diminished, and for patients surviving more than 2 years since starting zidovudine, the death rate was greater than for untreated patients who had developed AIDS at the same time (relative rate, 1.35; 95% CI, 1.15 to 1.58). Adjustment for other prognostic factors failed to substantially affect this observation. CONCLUSIONS: When initiated after the time of AIDS diagnosis, zidovudine was associated with improved prognosis but for no more than 2 years after starting therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Cigarette smoking as a potential cause of cervical cancer: has confounding been controlled?

It is widely believed that some sexually transmitted pathogen plays a key role in the aetiology of cervical cancer. However, although certain human papilloma viruses are strongly implicated, the pathogen responsible and its mechanism of action remain to be finally characterized. The correlation between cigarette smoking and sexual activity that exists in most cultures therefore makes evaluation of the potential additional role of smoking difficult, due to confounding with the presence of the aetiological pathogen. Epidemiological studies of the association between smoking and cervical cancer have adjusted for the lifetime number of sexual partners as a proxy measure of the presence of the pathogen and, in most cases, the association has diminished but remained statistically significant. Since the use of a proxy will tend to result in underestimation of the effect of the aetiological pathogen on risk of cervical cancer, however, the adjustment is likely to be insufficient, thus resulting in overestimation of the adjusted or 'independent' effect of smoking. In an attempt to address this concern we used a simulation approach to investigate whether a substantial 'independent' association between smoking and cervical cancer might be expected as a result of the use of a poor proxy for the aetiological pathogen, even if there is no true effect of smoking. Using realistic estimates of the association between the presence of the aetiological pathogen and both smoking and risk of cervical cancer, 'independent' relative risks for cigarette smoking of two and above were generated. It is therefore plausible that the observed 'independent' effect of cigarette smoking on cervical cancer is due to residual confounding.

Confounding Factors, Epidemiologic↗
PubMed1994

A sex comparison of rates of new AIDS-defining disease and death in 2554 AIDS cases. AIDS in Europe Study Group.

OBJECTIVES: To compare the development rate of new AIDS-defining diseases between 566 women and 1988 men with AIDS who were infected with HIV via the same routes (mainly by sharing drug injecting equipment and heterosexual sex). DESIGN: Information on patient follow-up after AIDS diagnosis was obtained by retrospectively reviewing case notes. METHODS: The 2554 men and women were followed from the time of AIDS diagnosis as part of the multicentre AIDS in Europe study, which examined AIDS cases diagnosed at 52 centres in 17 European countries between 1979 and 1989. Incidence of AIDS-defining diseases and demographic variables were recorded for all patients and CD4 lymphocyte count at the time of AIDS diagnosis for approximately half the patients. RESULTS: Only toxoplasmosis and herpes simplex virus ulceration showed statistically significant differences in occurrence rate between women and men [relative risks (RR), 1.51 and 3.44; 95% confidence interval (CI), 1.51 1.09-2.08 and 3.44 1.92-6.23, respectively] which remained after adjusting for imbalances in other variables. For both diseases, the additional absolute rate in women was approximately three per 100 person-years at risk. Survival after AIDS diagnosis was also similar between the two sexes (RR, 0.96; 95% CI, 0.86-1.08). CONCLUSION: There appears to be little difference between women and men in the clinical course of AIDS.

AIDS-Related Opportunistic Infections↗