Mci Lipman

Paradoxical reactions during tuberculosis treatment in patients with and without HIV co-infection

Background: It has been suggested that deterioration of tuberculosis (TB) during appropriate treatment, termed a paradoxical reaction (PR), is more common and severe in HIV positive individuals on highly active antiretroviral therapy (HAART). Method: A study was undertaken to determine the frequency of PR and its associated features in a population of HIV+TB+ patients and a similar sized group of HIV−TB+ individuals. Results: PR occurred in 28% of 50 HIV+TB+ patients and 10% of 50 HIV−TB+ patients. Disseminated TB was present in eight of 13 HIV+TB+ patients and four of five HIV−TB+ patients with PR. In 28 HIV+TB+ patients starting HAART, PR was significantly associated with commencing HAART within 6 weeks of starting antituberculosis treatment (p = 0.03) and was more common in those with disseminated TB (p = 0.09). No association was found between development of PR and baseline CD4 count or CD4 response to HAART. Conclusions: PR is common in HIV infected and uninfected individuals with TB. Early introduction of HAART and the presence of disseminated TB appear to be important in co-infected patients.

CD8+,CD38+ lymphocyte percent: a useful immunological marker for monitoring HIV-1-infected patients.

We investigated the relationship between three prognostic markers, CD4 lymphocyte count, serum beta2-microglobulin (beta2M) levels, and CD8+,CD38+ lymphocyte percent, and the association with the rate of development of AIDS. The markers were measured regularly throughout follow-up in 224 patients. The risk of developing AIDS during follow-up was investigated using Cox proportional hazards models. Time-updated values of the prognostic markers were used, which modelled the risk of AIDS according to the latest measurement of the marker rather than using a single value of the marker at baseline. During a median follow-up period of 13.6 months (range 0.5-31.9 months), 34 cases of AIDS occurred. In a univariate analysis, all three markers predicted the development of AIDS; a 10% increase in the percentage of CD8+ T cells expressing CD38+ resulted in an 88% increase in the risk of AIDS (95% confidence interval: 53-130%; p < 0.0001). After adjustment for the current CD4 count and beta2M, a 10% increase in the CD8+,CD38+ population was associated with a 37% increase in the risk of AIDS (95% confidence interval: 4-81%; p = 0.02). Thus, the percentage CD8+,CD38+ level predicts the development of AIDS independently of the latest CD4 count and beta2M. This assay is therefore potentially useful in conjunction with blood CD4 counts and serum beta2M levels in patient management and clinical trial design.

British HIV Association guidelines for the treatment of TB/HIV coinfection 2011

1.0 Summary of guidelines 2.0 Introduction 3.0 Aims of TB treatment 4.0 Diagnostic tests 5.0 Type and duration of TB treatment 6.0 Drug–drug interactions 7.0 Overlapping toxicity profiles of antiretrovirals and TB therapy 8.0 Drug absorption 9.0 When to start HAART 10.0 Directly observed therapy (DOT) 11.0 Management of relapse, treatment failure and drug resistance 12.0 Pregnancy and breast-feeding 13.0 Treatment of latent TB infection – HAART, anti-tuberculosis drugs or both? 14.0 Immune reconstitution inflammatory syndrome (IRIS) 15.0 Prevention and control of transmission 16.0 Death and clinico-pathological audit 17.0 Tables 18.0 Key points 19.0 References

Immune reconstitution pneumonitis following Pneumocystis carinii pneumonia in HIV‐infected subjects

An HIV‐infected man presented with a pneumonic illness following an episode of treated Pneumocystis carinii pneumonia (PCP). He had a rise in his CD4 count from 4 to 125 cells/µL on antiretroviral therapy prior to the onset of the second respiratory event. Bronchoalveolar lavage (BAL) revealed no pathogen, although a CD4 lymphocytosis in addition to a highly unusual population of rapidly proliferating CD8 cells was demonstrated. Following 2 weeks of steroid and anti‐pneumocystis therapy, a repeat bronchoscopy demonstrated that the expression of these markers had returned to low values. This second respiratory illness, which may have arisen as a consequence of the regenerating immune response reacting to residual P. carinii antigen in the lung, is apparently not rare. When we reviewed our case notes, five further individuals were identified that had started antiretroviral therapy following an episode of PCP and subsequently developed a self‐limiting pneumonitis for which no pathogen was identified on bronchoscopy.

Outbreak of isoniazid resistant tuberculosis in north London

Background: A description is given of a major outbreak of isoniazid monoresistant tuberculosis (TB) chiefly in north London, including prisons. The earliest case was diagnosed in 1995 with most cases appearing after 1999. Methods: Confirmation of a local cluster of cases was confirmed by restriction fragment length polymorphism (RFLP IS6110) typing or “rapid epidemiological typing” (RAPET). Further cases were found by retrospective analysis of existing databases, prospective screening of new isolates, and targeted epidemiological case detection including questionnaire analysis. Results: By the end of 2001, 70 confirmed cases in London had been linked with a further 13 clinical cases in contacts and nine epidemiologically linked cases outside London. The epidemic curve suggests that the peak of the outbreak has not yet been reached. Cases in the outbreak largely belong to a social group of young adults of mixed ethnic backgrounds including several individuals from professional/business backgrounds. Compared with other cases of TB reported to the enhanced surveillance scheme in London during 1999–2001, the cases are more likely to be of white (26/70 (37%) v 1308/7666 (17%)) or black Caribbean ethnicity (17/70 (24%) v 312/7666 (4%)), born in the UK (41/70 (59%) v 1335/7666 (17%)), and male (52/70 (74%) v 4195/7666 (55%)). Drug misuse and/or prison detention are factors common to many cases. Conclusions: The investigation of the outbreak revealed significant problems on an individual patient and population based level including difficulties with contact tracing, compliance, and the risk of developing multidrug resistance. This incident has demonstrated the value of molecular strain typing in investigating an extensive outbreak of TB. This is the first documented outbreak involving a UK prison.

BHIVA treatment guidelines for tuberculosis (TB)/HIV infection 2005

AL Pozniak, RF Miller, MCI Lipman, AR Freedman, LP Ormerod, MA Johnson, S Collins and SB Lucas, on behalf of the BHIVA Guidelines Writing Committee Chelsea and Westminster NHS Healthcare Trust, London, UK, Centre for Sexual Health and HIV Research, Department of Primary Care and Population Sciences, Royal Free and University College Medical School, University College London, London, UK, Royal Free Hospital, London, UK, Cardiff University School of Medicine, Cardiff, UK, Blackburn Royal Infirmary, Blackburn, Lancashire, UK, HIV i-Base, London, UK, Department of Histopathology, GKT School of Medicine, St Thomas’ Hospital, London, UK

Virological Response to Highly Active Antiretroviral Therapy Is Unaffected by Antituberculosis Therapy

We compared 156 human immunodeficiency virus (HIV)-infected patients who had tuberculosis with control populations of similar size. Of 111 patients with HIV infection and tuberculosis who received highly active antiretroviral therapy (HAART) and therapy for tuberculosis concurrently, 92 (83%) achieved or maintained virus loads of <50 copies/mL, and 99 (89%) achieved or maintained a >or=2 log10 reduction in virus load after 6 months. Virological response and changes in CD4 cell count were equivalent to those in 111 matched HIV-infected subjects without tuberculosis starting HAART. Tuberculosis recurrence rates were similar to those found in an HIV-uninfected population of 156 subjects (3% and 1%, respectively). Treatment for HIV and tuberculosis does not compromise outcomes for either disease.

Cardiovascular disease risk factors and antiretroviral therapy in an HIV-positive UK population

Although the benefits of antiretroviral therapy (ART) have been dramatic, studies have started to report a variety of drug‐related side effects and toxicities. We sought to characterize the risk factors for cardiovascular disease present in an HIV‐positive population.

STAGING SYSTEM FOR CLINICAL AIDS PATIENTS

Although there are wide differences in prognosis between patients with AIDS they are often thought of as a single homogeneous group. We think a simple staging system that accounts for important prognostic factors including type and number of AIDS diseases and the CD4 lymphocyte count is required. We followed 363 AIDS patients at the Royal Free Hospital and reported the occurrence of 680 AIDS-defining diseases (ADDs). We measured CD4 counts at approximately monthly intervals. Severity of AIDS diseases was defined a priori on the basis of survival in the AIDS in Europe study of 6578 AIDS patients: mild-oesophageal candidiasis, Kaposis sarcoma (cutaneous), Pneumocystis carinii pneumonia, extrapulmonary tuberculosis; severe-all other ADDs except lymphoma; very severe-lymphoma. The risk of death increased by 15% (p = 0.08) for each mild condition experienced, by 89% (p < 0.0001) for each new severe condition and by 535% (p < 0.0001) when a lymphoma developed. Estimates from the Cox model were used to derive a score reflecting the risk of death. Patient experience was divided into three categories. Patients in AIDS Grade I had an average death rate of one per 10.1 years, compared with one per 2.8 years in AIDS Grade II and one per 1.1 years in AIDS Grade III. Similar rates were seen in an independent validation study on 1230 AIDS patients at different hospital. Our grading system should be useful for patient management, clinical trial design, surveillance, and resource management.

An audit of antiretroviral treatment use in HIV‐infected patients in a London clinic: the limitations of observational databases when auditing antiretroviral treatment use

To audit the use of antiretroviral (ARV) treatment in a large treatment clinic in the UK against the British HIV Association (BHIVA) ARV treatment guidelines.