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Biomedical subjects

S Madge

Publications and source records attributed to S Madge.

At least 19 recordsLinked to original sources
PubMed2001

Gender differences in virologic response to treatment in an HIV-positive population: a cohort study.

OBJECTIVE: To establish whether a gender difference in virologic response to highly active antiretroviral treatment (HAART) exists. METHODS: A cohort of HIV-positive individuals was examined. OUTCOMES: Achievement of viral load <500 copies/ml and "failure" (failure to suppress viral load <500 copies/ml after 24 weeks or two consecutive measurements above this level after having suppressed below it). Hazard ratios (HRs) comparing the rate in women to that in men were derived using the Cox model. RESULTS: Of 366 male subjects, 79% were white and 82% were homosexual. Sixty-three percent of the 91 female subjects were African and 87% were heterosexual. The median follow-up after HAART was 94 weeks. The baseline CD4 count was higher in men (228 x 106 per liter) than in women (171 x 106 per liter) (p =.01), but the viral load was similar (p =.88). The median time to <500 copies/ml was 16 weeks. Women achieved a viral load of <500 copies/ml at a faster rate than men, with an adjusted HR of 1.46 (95% confidence interval [CI]: 0.99-2.16; p =.06). Some 261 patients failed treatment (58% of men and 53% of women) with an HR of 0.78 (95% CI: 0.51-1.21; p =.27). CONCLUSIONS: Women may achieve virologic suppression at a faster rate than men and have a more durable response. Further research should examine these responses in conjunction with clinical outcomes, because gender differences in virologic response may ultimately be of little relevance if clinical outcomes are similar.

Adult↗
PubMed2001

Reasons for modification and discontinuation of antiretrovirals: results from a single treatment centre.

OBJECTIVE: To describe the reasons for, and factors associated with, modification and discontinuation of highly active antiretroviral therapy (HAART) regimens at a single clinic. SUBJECTS: A total of 556 patients who started HAART at the Royal Free Hospital were included in analyses. Modification was defined as stopping or switching any antiretrovirals in the regimen, whereas discontinuation was defined as the simultaneous stopping of all antiretrovirals included in the initial regimen. Reasons were classified as immunological/virological failure (IVF) and toxicities and patient choice/poor compliance (TPC). RESULTS: The median CD4 count at starting HAART was 171 x 10(6) cells/l and viral load 5.07 log copies/ml. During a median follow-up of 14.2 months, 247 patients (44.4%) modified their HAART regimen, 72 due to IVF (29.1%) and 159 due to TPC (64.4%) and a total of 148 patients (26.6%) discontinued HAART. Older patients were less likely to modify HAART [relative hazard (RH), 0.73 per 10 years; P = 0.0008], as were previously treatment-naive patients (RH, 0.65; P = 0.0050), those in a clinical trial (RH, 0.64; P = 0.027) and those who started nelfinavir (RH, 0.57; P = 0.035). Patients who started with four or more drugs (RH, 2.21, P < 0.0001), who included ritonavir in the initial regimen (RH, 1.41; P = 0.035) or who had higher viral loads during follow-up (RH per log increase, 1.51; P < 0.0001) were more likely to modify HAART. CONCLUSIONS: There was a high rate of modification and discontinuation of HAART regimens in the first 12 months, particularly due to toxicities, patient choice or poor compliance.

Antiretroviral Therapy, Highly Active↗
PubMed2000

Changes in CD4 lymphocyte counts after interruption of therapy in patients with viral failure on protease inhibitor-containing regimens. Royal Free Centre for HIV Medicine.

OBJECTIVE: To describe the short-term changes in CD4 lymphocyte counts after the interruption of antiretroviral HIV therapy in order to increase the understanding of CD4 lymphocyte dynamics, and so that appropriate monitoring strategies can be designed. METHODS: We studied 35 HIV-infected patients with late-stage disease who had therapy interruptions leading to high viral load levels, median greater than 750 000 RNA log10 copies/ml, and in whom two CD4 cell counts (median 28 days apart) were available before beginning a salvage regimen. RESULTS: Overall, there was a substantial decline in CD4 cell counts from a median of 125 to 83 cells/mm3 in the average 28 day period, with median proportionate and absolute losses of 26% and 24 cells/mm3 per month, respectively (P < 0.008). This tended to be greater in individuals studied sooner after interrupting therapy (P = 0.03) and in those with CD4 cell counts above the pre-therapy baseline (P = 0.06). There was a strong negative correlation between the proportionate increase in viral load and the absolute change in CD4 cell count (-0.66, P = 0.0002). CONCLUSION: Patients with relatively advanced HIV infection interrupting antiretroviral therapy after failing a protease inhibitor-containing regimen require frequent monitoring because CD4 cell counts appear to fall quite rapidly, at least in the first few weeks after interruption.

Adult↗
PubMed2000

Immunological, virological and clinical response to highly active antiretroviral therapy treatment regimens in a complete clinic population. Royal Free Centre for HIV Medicine.

BACKGROUND: Highly active antiretroviral therapy (HAART) is now widely used in clinical practice and gives rise to a range of immunological, virological and clinical responses. OBJECTIVES: To describe the immunological, virological and clinical response to HAART and to examine the frequency of modification of the HAART regimen among patients from a single treatment centre. METHODS: Kaplan-Meier estimation and incidence rates were used to describe responses to HAART (a protease inhibitor or non-nucleoside drug in addition to at least two nucleoside analogues) among 421 patients from the Royal Free Hospital in London. RESULTS: The median CD4 cell count at starting HAART was 186 x 10(6) cells/l [interquartile range (IQR) 76-310] and viral load was 5.13 log10 copies/ml (IQR 4.66-5.56). At 6 months after starting HAART, 51.1% of patients were estimated to have experienced a 100 x 10(6) cells/l increase in CD4 cell count; the median time for viral load to fall below 400 copies/ml was 3.7 months (95% confidence interval 3.2-4.4). At 6 months after the first viral load was < 400 copies/ml, 16.4% of patients were estimated to have failed on the basis of a single viral load > 400 copies/ml and 12.4% were estimated to have failed if the more stringent definition of two viral loads above the limit of detection was used. Compared with the pre-HAART era, the incidence of death among patients on HAART was one sixth of that level; new AIDS-defining illnesses was one seventh; and hospital admissions was one fifth. In total, 141 patients (33.5%) stopped at least one of the antiretroviral agents included as part of their HAART regimen; the occurrence of side effects was the most common reason (n = 63; 44.7%). CONCLUSION: A good response occurred to an initial HAART regimen. There was a high rate of virological relapse, which varied considerably according to the definition of failure used. Even so, the rates of clinical progression and hospital admissions observed to date were low. Further follow-up of these patients is required to determine their long-term immunological, virological and clinical outcome.

Anti-HIV Agents↗
PubMed2000

Multidisciplinary teams in the United Kingdom: problems and solutions.

Creating a team requires a clear strategy with objectives and boundaries. Teams succeed or fail depending on the enthusiasm and dedication of the members. Important points to consider in maintaining effectiveness include team philosophy, leadership, dynamics, communication, and workload. Members provide a unique contribution that must be valued and respected. Maintaining a productive and friendly team can become difficult. Issues such as uncertainty of the team's position in the overall service, caseload, poor coordination between team members, and uneven work distribution may cause disruption. To ensure a functioning and useful team, members must be constantly aware of their working relationships with each other and the impact they have on patients, families, and colleagues.

Child↗
PubMed1999

A comparison of exposure groups in the EuroSIDA study: starting highly active antiretroviral therapy (HAART), response to HAART, and survival.

BACKGROUND: Concerns have been raised that intravenous drug users may be less likely to start highly active antiretroviral therapy (HAART) and that adherence to therapy may be poor among this group of patients. Given the decreased mortality and incidence of AIDS-defining illnesses among patients with HIV who start HAART, this may lead to a poorer prognosis among intravenous drug users. PURPOSE: To compare homosexual men, intravenous drug users, and heterosexuals in EuroSIDA, a prospective European cohort of 7331 patients with HIV in terms of starting a HAART treatment regimen, immunologic and virologic response to therapy, and survival. METHODS: 6645 patients were included in this analysis. Logistic regression and Cox proportional hazards models were used to investigate the factors associated with use of HAART regimens and survival following recruitment to the EuroSIDA study. RESULTS: In a multivariate logistic regression model, intravenous drug users were significantly less likely to be receiving HAART at recruitment to EuroSIDA (odds ratio [OR], 0.48; 95% confidence interval [CI], 0.37-0.62; p<.0001) when compared with homosexual men. Similarly, during follow-up, intravenous drug users were at a 27% reduced risk of starting HAART, after adjustment for other factors related to starting HAART (relative hazard [RH], 0.73; 95% CI, 0.64-0.82; p<.0001). There were no differences between heterosexual and homosexual patients, and similar results were found within regions of Europe (South, Central and Northern). Among those patients who started HAART, there were no significant differences between exposure groups in CD4 lymphocyte count response to HAART or virologic response to HAART. After adjustment for factors related to survival, intravenous drug users were at a small, but nonsignificant increased risk of death compared with homosexuals (RH 1.16; 95% CI, 0.99-1.38; p = .074). CONCLUSIONS: Intravenous drug users were significantly less likely to start HAART, but among those who did, response to therapy was similar to that of other exposure groups. There were no differences in risk of death. If intravenous drug users continue to use HAART less commonly than other exposure groups, it may result in a poorer prognosis, a different spectrum of AIDS-defining illnesses, and differential long-term clinical needs.

Adult↗
PubMed1999

Changes in AIDS-defining illnesses in a London Clinic, 1987-1998.

OBJECTIVES: To describe the incidence of AIDS-defining illnesses within a single large clinic setting, to describe temporal changes over a 10-year period in the overall incidence and of individual AIDS-defining illnesses and to investigate the impact of HIV treatment regimen on the incidence of AIDS-defining illnesses. SUBJECTS AND METHODS: A person-years analysis was used to determine the incidence of AIDS-defining illnesses according to calendar year and stratification by CD4 lymphocyte count and treatment regimen in 1806 patients from the Royal Free Centre for HIV Medicine with at least one CD4 lymphocyte count and follow-up visit. RESULTS: Prior to 1992, the incidence of all AIDS-defining illnesses was 27.4/100 person-years of follow-up (PYFU; 95% confidence interval [CI], 22.8-32.0) and during 1997 this incidence had dropped to 6.9/100 PYFU (95% CI, 4.7-9.1; p < .0001, test for trend). The decline in incidence over time occurred in esophageal candidiasis, cytomegalovirus disease (including retinitis), Kaposi's sarcoma, lymphoma, wasting syndrome, and Pneumocystis carinii pneumonia (p < .05, test for trend), but there was no evidence of a decline in AIDS dementia or in Mycobacterium avium complex. In 1997, among patients with CD4 lymphocyte counts of < or =200 cells/mm3, the incidence rates for any AIDS-defining illness was 51.1/100 PYFU for patients taking no therapy (95% CI, 27.9-85.7), 34.5 among patients on monotherapy (95% CI, 4.2-124.6), 13.2 among patients taking dual combination therapy (95% CI, 3.6-33.8) and 6.1 among patients taking triple therapy or more complex regimens (95% CI, 0.7-22.0; p < .0001, test for trend). CONCLUSIONS: There was a considerable decline in AIDS-defining illnesses during 1996 and 1997, coinciding with the rapid development of new antiretroviral treatments and combinations of treatment. Further follow-up of large observational cohorts is essential to monitor the incidence of diagnoses less common than we were able to consider, such as tuberculosis, cryptosporidiosis, and cryptococcosis, and also to investigate whether the incidence of disease continues to fall, or whether it starts to rise again, as toxicities, compliance, drug resistance, and long-term side effects begin to appear.

AIDS Dementia Complex↗
PubMed1999

In vivo HIV-1 replicative capacity in early and advanced infection.

OBJECTIVE: Previous studies on patients treated with potent antiretroviral therapy have shown that viral clearance rates do not tend to change between early and advanced HIV-1 infection. Our objective was to investigate whether the other major aspect of virus dynamics, viral replicative capacity, does change. In vitro work has indicated that the viral replicative, capacity increases but in vivo evidence has been lacking. METHODS: As an in vivo measure of the viral replicative capacity, we studied the rate of rebound of plasma HIV RNA level during a 1-week therapy interruption in previously untreated patients who had received 2 weeks of antiretroviral therapy. RESULTS: Such therapy in five previously drug-naive patients with high CD4 lymphocyte counts (mean, 611 x 10(6)/l) and five patients with low counts (mean, 49 x 10(6)/l) led to a mean 2.2 log10 copies/ml decrease in plasma HIV-1 levels (from 5-6 log10 copies/ml) in 2 weeks. This was similar in the two groups. Interruption of therapy for the ensuing week resulted in a stable HIV-1 level for approximately 2 days followed by a rebound towards pretherapy level, which was much more marked in the patients with low CD4 cell counts (estimated mean rise 2.22 log10 versus 1.06 log10 copies/ml; P < 0.02). After restarting therapy, HIV RNA levels returned to pre-interruption levels. CONCLUSIONS: These findings need confirmation, but the ability of HIV-1 to replicate in vivo appears to increase during HIV-1 infection. This increased replicative capacity, for which there are several potential explanations, may be the cause of gradual CD4 lymphocyte depletion.

HIV Infections↗
PubMed1999

Do people attending a same day testing clinic discuss their need for a HIV test with their GP?

In the United Kingdom, people with HIV infection present with advanced disease and general practitioners (GPs) are currently an underused resource for HIV testing. We describe the reasons for using an open-access clinic rather than primary care for testing for HIV. People attending the clinic were asked to complete a questionnaire asking about GP registration, access, and whether HIV testing was discussed in primary care. Despite access to GPs, HIV testing in primary care was rarely discussed. If HIV testing is to move to a general practice setting, GPs could address the issues, such as the recording of sensitive information in notes, future life insurance, and confidentiality, which this report identifies as the main barriers for using primary care.

Family Practice↗
PubMed1998

Demographic, clinical and social factors associated with human immunodeficiency virus infection and other sexually transmitted diseases in a cohort of women from the United Kingdom and Ireland. MRC Collaborative Study of women with HIV.

BACKGROUND: Clinical experience suggests many women with HIV infection have experienced no other sexually transmitted diseases (STD). Our objective was to test the hypothesis that a substantial proportion of women with HIV infection in the United Kingdom and Ireland have experienced no other diagnosed STD and to describe the demographic, clinical and social factors associated with the occurrence of other STD in a cohort of HIV infected women. METHOD: Analysis of cross-sectional baseline data from a prospective study of 505 women with diagnosed HIV infection. The setting was 15 HIV treatment centres in the United Kingdom and Ireland. The main outcome measures were occurrence of other STD diagnosed for the first time before and after HIV diagnosis. Data were obtained from interview with women and clinic notes. We particularly focused on occurrence of gonorrhoea, chlamydia and trichomoniasis after HIV diagnosis, as these are the STD most likely to reflect recent unprotected sexual intercourse. RESULTS: The women were mainly infected via heterosexual sex (n = 304), and injection drug use (n = 174). 151 were black Africans. A total of 250 (49.5%) women reported never having been diagnosed with an STD apart from HIV, 255 (50.5%) women had ever experienced an STD besides HIV, including 109 (21.6%) who had their first other STD diagnosed after HIV. Twenty-five (5%) women reported having had chlamydia, gonorrhoea or trichomoniasis diagnosed for the first time after HIV diagnosis, possibly reflecting unprotected sexual intercourse since HIV diagnosis. In all 301 (60%) women reported having had sex with a man in the 6 months prior to entry to the study. Of these, 168 (58%) reported using condoms 'always', 66(23%) 'sometimes' and 56 (19%) 'never'. CONCLUSIONS: Half the women in this study reported having never experienced any other diagnosed STD besides HIV. However, after HIV diagnosis most women remain sexually active and at least 5% had an STD diagnosed which reflect unprotected sexual intercourse.

Adolescent↗
PubMed1998

Research bronchoscopies do not adversely affect HIV-infected individuals' future health-care decisions.

STUDY OBJECTIVES: Asymptomatic HIV-infected individuals are increasingly recruited for studies involving invasive procedures such as bronchoscopy. We sought to determine the response to and outcome of a request for a research bronchoscopy in HIV-positive individuals with no respiratory disease, and whether this would adversely affect future decisions to have a medically indicated bronchoscopy. DESIGN AND SETTING: Prospective, semistructured, questionnaire-based study in a London teaching hospital HIV outpatient clinic. PARTICIPANTS: One hundred and seven consecutive HIV-infected eligible individuals. Thirty-one healthy volunteers served as a control group for the subjective response to bronchoscopy. MAIN OUTCOME MEASURES: Subjects' attitudes and responses to requests for bronchoscopy and subsequent behavior when they required medically indicated bronchoscopy. RESULTS: Seventy-five patients (70%) agreed to the procedure in principle, predominantly for altruistic reasons. Thirty-nine subjects underwent bronchoscopy. Five percent found it worse than expected; and 79% agreed to another research bronchoscopy (performed in 11 subjects approximately 2 years later). All patients said they would undergo bronchoscopy again for diagnostic purposes (required in seven during the study). When compared to a healthy volunteer population within the same study, postbronchoscopy symptoms were similar in frequency although somewhat different in nature. Subjects felt that a clear explanation of what was involved enhanced their participation in this research. CONCLUSIONS: Invasive research procedures such as bronchoscopy can be performed and are repeatable in a healthy HIV-infected population. Performance of procedures for research purposes does not appear to adversely affect future health-care decisions.

Adolescent↗
PubMed1998

HIV.

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Family Practice↗