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Biomedical subjects

S Mandalia

Publications and source records attributed to S Mandalia.

At least 37 records · Page 2Linked to original sources
PubMed2003

Restoration of human immunodeficiency virus-1-specific responses in patients changing from protease to non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy.

The effect of altering antiretroviral therapy (ART) on responses to viral, recall and human immunodeficiency virus (HIV)-1-specific recombinant antigens and interleukin-2 (IL-2) in HIV-1-infected patients was assessed. A longitudinal cohort study in eight HIV-1 infected individuals following a clinically indicated therapy change (seven for drug intolerance and one for virological failure) from protease inhibitor (PI) to non-nucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral regimens was performed. CD4 T-cell counts, viral loads, lymphoproliferative responses, cytokine production and latent proviral deoxyribonucleic acid (DNA) were measured at baseline and at weeks 12 and 24 after therapy substitution. Following therapy-switch there was a 33% proportional increase in mitogen response (95% confidence interval (CI), 3-33%) and a 31% increase (95% CI, 15-48%) in viral and recall-antigen responses. Six patients developed proliferative responses to low concentration IL-2 stimulation. All patients demonstrated an increase in median HIV-1-specific responses, as three had detectable virus at baseline (two being viral rebound); this may reflect an autovaccination effect. Proviral DNA changes largely reflected plasma HIV-1 ribonucleic acid (RNA). In conclusion, NNRTI substitution for a PI may favour immune reconstitution with an improvement in HIV-1-specific responses, which may reflect differential effects on antigen processing and presentation, an autovaccination effect or alternatively a potential suppressive effect of the PI.

Anti-HIV Agents↗
PubMed2003

The prevalence of reduced zidovudine susceptibility in zidovudine-naive, antiretroviral-experienced HIV-1-infected patients.

OBJECTIVES: There is increasing in vitro and in vivo evidence that reduced zidovudine (ZDV) susceptibility is generated by the selective pressure conferred by other nucleoside reverse transcriptase inhibitors (NRTIs). However, the degree to which this occurs in clinical practice remains unclear. We assessed phenotypic and genotypic resistance in ZDV-naive patients with virological failure on stavudine (d4T)-containing regimens, with particular reference to potential cross-resistance between d4T and ZDV. METHODS: Patients were identified from a clinical database. Treatment history was confirmed by case note evaluation and discussion with patients. Genotypic and phenotypic analyses were undertaken by Virco (Virco BVBA, Mechelen, Belgium). RESULTS: Sixty-seven drug-experienced, ZDV-naive patients who underwent a resistance test while failing a d4T-containing regimen were identified. Of these patients, 23% had received three or more NRTIs and 42% at least one non-nucleoside reverse transcriptase (RT) inhibitor; 22% had viruses with reduced d4T susceptibility (>1.8-fold resistance), and 25% had viruses with reduced ZDV susceptibility (>4-fold). The most frequently observed RT mutations were identified. A significant correlation was found between susceptibility to d4T and susceptibility to ZDV (r=0.36; P=0.003), and also between virtual resistance to d4T and that to ZDV (r=0.38; P=0.002). CONCLUSIONS: A significant minority of d4T-treated, ZDV-naive patients were found to have viruses with reduced ZDV susceptibility, with a variable association with classical ZDV resistance mutations. These data suggest that cross-resistance between d4T and ZDV may involve novel constellations of mutations. Correlations between d4T and ZDV susceptibilities and resistances further support cross-resistance between NRTIs.

Anti-HIV Agents↗
PubMed2003

Matched case-control study to evaluate risk factors for hyperlactataemia in HIV patients on antiretroviral therapy.

BACKGROUND: Lactic acidosis is a life-threatening event during antiretroviral therapy (ART). Hyperlactataemia may be a prelude to acidosis. Our database study suggested that female gender, intercurrent illness and didanosine (ddI)-based regimens may increase risk of lactic acidosis. The aim of this matched case-control study was to identify risk factors for hyperlactataemia requiring screening. METHODS: Cases were defined as patients with two consecutive lactate samples > or =3.5 mmol/L taken more than 1 week apart. Cases were matched to two controls on gender, use of ddI and total duration of therapy using a 6-month window on either side. Controls never had raised lactate >2.5 mmol/L. A conditional logistic regression analysis using the PHREG procedure in SAS (SAS Institute Inc, Cary, NC) was performed with a discreet logistic model stratified by matching variables. RESULTS: Twenty-one cases were matched to 42 controls. In the univariate model, current use of stavudine (d4T), total cholesterol >5.3 mmol/L and glucose levels > or =5.2 mmol/L gave increased likelihood of persistent hyperlactataemia. The multivariate model showed current use of d4T to be a significant independent predictor of persistent hyperlactataemia. CONCLUSIONS: The results of this case-control study indicate that, when controlling for ddI use, d4T use is an additional risk factor for hyperlactataemia.

Acidosis, Lactic↗
PubMed2003

Paclitaxel for anthracycline-resistant AIDS-related Kaposi's sarcoma: clinical and angiogenic correlations.

BACKGROUND: Murine data indicate that angiogenesis is central to the aetiopathogenesis of Kaposi's sarcoma (KS). Therefore, we measured angiogenic cytokines and growth factors in patients with AIDS-related KS during treatment with both antiretrovirals and second-line paclitaxel chemotherapy. Cytokines measured included tumour necrosis factor-alpha (TNF-alpha), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and the interleukins IL-2, -6 and -12. PATIENTS AND METHODS: Enzyme-linked immunosorbent assays (ELISAs) were carried out to measure plasma cytokine levels in 17 patients with AIDS-related KS who had progressed within 6 months of receiving liposomal anthracyclines and were treated with paclitaxel 100 mg/m(2) every 2 weeks. Measurements were carried out before progression, at commencement and at the completion of paclitaxel. RESULTS: The objective response rate to paclitaxel was 71% (95% confidence interval 60% to 81%). In 17 patients with AIDS-related KS, we observed eight partial responses and four complete responses. Patients with AIDS Clinical Trial Group stage T1 disease had higher plasma VEGF (P = 0.05) and lower plasma TNF-alpha levels (P = 0.05) than patients with earlier stage T0 KS. There were no correlations between plasma cytokines (bFGF, VEGF, TNF-alpha, and IL-2,-6 and -12) and the CD4 and CD8 cell counts or HIV-1 RNA viral load. Response to paclitaxel was associated with a fall in plasma IL-6 levels (P = 0.04) but no change in other cytokines. There were no significant changes in CD4, CD8, CD16/56, CD19 cell counts and HIV-1 viral loads during chemotherapy. CONCLUSIONS: Angiogenic cytokines may correlate with KS disease extent but not with cellular immune function or HIV viraemia. Response to paclitaxel therapy correlates with a fall in plasma IL-6 levels and recent data indicate this may be a surrogate marker of KS-associated herpesvirus viral load. Overall, clinical response in KS correlates poorly with known angiogenic cytokines.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Endoscopic balloon dilatation versus endoscopic sphincterotomy for the removal of bile duct stones: a prospective randomised trial.

BACKGROUND: Endoscopic balloon dilatation (EBD) of the sphincter of Oddi has been proposed as an alternative therapy with possible advantages, as compared with endoscopic sphincterotomy (ES), for removal of bile duct stones. PATIENTS AND METHODS: In a randomised study, we compared the efficacy and complication rate of the two techniques in 202 patients with common bile duct stones. Patients were followed up for 12 months. RESULTS: A total of 103 patients were randomised to the EBD group and 99 to the ES group. Overall duct clearance was 87.1% and did not differ between the two groups (EBD 87.4%; ES 86.9%). The complication rate at 24 hours was 6.8% in the EBD group and 3.0% in the ES group (NS). Complications during follow up were 11.7% and 15.2% respectively (NS). A multivariate logistic regression analysis showed only the size of the largest stone to be predictive of success for either technique. CONCLUSION: Endoscopic balloon dilatation offers no significant advantage over the well established technique of endoscopic sphincterotomy for the removal of bile duct stones.

Aged↗
PubMed2003

Is increased surveillance for asymptomatic syphilis in an HIV outpatient department worthwhile?

OBJECTIVES: Syphilis outbreaks have recently been reported in the United Kingdom, some of which have included cohorts of HIV positive individuals. As a result we commenced 3 monthly screening of syphilis serology (STS) for HIV positive patients having routine follow up blood tests. We assessed if there was an increased number of individuals being screened and also whether the screening programme was diagnosing early cases of syphilis. METHODS: Data from a 1 year period following introduction of screening (May 2001) were analysed and compared with data from the same period last year. The case notes of patients with a positive VDRL were reviewed to establish, firstly, whether these represented new diagnoses and, secondly, whether patients were asymptomatic at the time of screening. RESULTS: 2670 patients had at least one CD4 count measured in the period (surrogate for patients having routine bloods). Of these, 2266 patients had STS performed (85%). 38 patients had a positive VDRL. Of these, 20 were confirmed as having early syphilis which was asymptomatic at the time of screening. Six asymptomatic cases were also confirmed with newly positive TPPAs and a negative VDRL. These 26 asymptomatic cases represent 29% of all cases of early syphilis diagnosed in our department and 50% of cases in the HIV positive cohort. CONCLUSION: With intensive surveillance significant numbers of cases of asymptomatic early syphilis are being identified in a group of HIV individuals under routine follow up, at an earlier stage than would otherwise have been the case. This presents an opportunity to intervene not only to prevent clinical illness but also to institute infection control measures.

AIDS-Related Opportunistic Infections↗
PubMed2002

Naively changing HAART.

BACKGROUND: Few UK studies have systematically investigated which antiretroviral therapy (ART) combinations HIV-infected people are commenced on, when they start and reasons for stopping or changing their regimens. OBJECTIVE: To describe when HIV-infected ART-naive patients started first-, second- or third-line triple ART, classes of drugs prescribed and whether stopping ART was associated with virological, immunological or clinical indicators of treatment failure. DESIGN: A multicentre prospective open cohort study, employing the National Prospective Monitoring System on the use, cost and outcome of HIV service provision in UK hospitals-HIV Health-economics Collaboration (NPMS-HHC). SETTING: Five hundred and eighty-five ART-naive patients seen in one London and two non-London HIV clinics between 1 January 1998 and 31 December 1999. RESULTS: Of 4,044 HIV-infected individuals seen, 585 (15%) were ART naive. Median time interval (interquartile range, IQR) between HIV diagnosis and starting triple ART was 800 (63-2,094) days. Median CD4 count when first diagnosed with HIV infection was 278 (IQR 127-481) cells/ micro L which dropped to 190 (IQR 86-297) cells/ micro L when starting triple ART. Of these 585 patients, 162 started second-line and 46 third-line ART during the study period. Of those patients who stopped ART, 51% did not have evidence of virological, immunological or clinical indicators of therapy failure. CONCLUSIONS: Reasons for the delay between diagnosis of HIV infection and starting ART are varied. The large proportion of individuals who stopped ART for reasons other than virological, immunological or clinical indicators of therapy failure, are most likely due to drug-associated toxicity. Both of these findings need to be elucidated in greater detail through prospective studies.

Adult↗
PubMed2002

Can targeted HIV testing campaigns alter health-seeking behaviour?

This paper describes the evaluation of 'gimme 5 minutes' a multimedia HIV testing campaign aimed at gay and bisexual men in London particularly targeting those of Black and South European Origin and those under the age of 25 years old using peer images. The text linked a summary of the key issues of a pre-test discussion with detailed information on how to access testing at a specified testing centre (campaign clinic). The number and demographics of men who reported sex with men (MSM) testing at the campaign clinic were monitored and compared with those testing at two other central London clinics. There was a 4.5-fold rise (p < 0.001) in MSM testing at the campaign clinic. Increases were proportionately greater in the sub-populations targeted with peer images: South European origin, 14-fold rise (p < 0.001), Black origin, 6.5-fold rise (p = 0.003), and MSM under 25 years old, 9.5-fold rise (p < 0.001). There were no significant changes in the number of MSM testing for HIV at the two other central London clinics studied. The results suggest that including detailed information about accessing testing services may be a vital ingredient in the success of media campaigns focusing on HIV testing.

Bisexuality↗
PubMed2002

Young people's views on provision of sexual health services.

OBJECTIVES: To identify the sexual health needs of young people in order to establish a service suited to these needs. METHODS: A peer designed questionnaire piloted to a small group of young people was followed by a more widely distributed, amended questionnaire. The questionnaire survey was delivered to 744 pupils aged 11-18 years in six secondary schools and a pupil exclusion unit in central London. Factors encouraging or discouraging the use of young people's sexual health services were measured. RESULTS: Several findings challenged existing models of care for young people's sexual health services. Notably, pupils wanted clinics to run more frequently than the usual once a week; the staff attributes that were most important were attitudinal rather than to do with sex, age, or physical appearance; and they did not mind if the waiting room contained older people. Many findings, however, agreed with existing data-young people wanted the clinic to be open after school; girls preferred to attend with a friend; a confidential, walk-in service was preferred. CONCLUSIONS: Large financial outlays are not necessary for the establishment of effective sexual health services for young people. Existing facilities and staff may be utilised with training of these staff to be sensitive to, and aware of, the needs of young people. Clinic opening times should coincide with school closing times. Although pupils stated a preference for female staff, this was not a high priority. More important was feeling that staff would listen to them and take their problems seriously, and that confidentiality would be maintained.

Adolescent↗
PubMed2001

Dietary advice with or without pravastatin for the management of hypercholesterolaemia associated with protease inhibitor therapy.

BACKGROUND: Therapy with a HIV protease inhibitor is associated with elevations in cholesterol and triglycerides. HMG-CoA reductase inhibitors ('statins') are the established therapy for persons with primary hypercholesterolaemia. Because of drug interactions, pravastatin may represent the preferred choice in those taking HIV protease inhibitors. DESIGN: A randomized, open-label comparative 24 week trial of dietary advice alone or with pravastatin in 31 male patients established on protease inhibitor-based regimens for greater than 12 weeks with viral load < 500 copies/ml and cholesterol > 6.5 mmol/l. RESULTS: There were no significant clinical or laboratory events and no patient discontinuation secondary to adverse effects. Viral rebound did not occur. Relative to baseline, total cholesterol at week 24 fell significantly in the pravastatin (1.2 mmol/l; 17.3%) (P < 0.05) but not in the dietary advice (0.3 mmol/l; 4%) group. The difference between the two groups approached significance at week 24 (P = 0.051). This fall was accounted for entirely by a reduction in low density lipoprotein [calculated change 1.24 mmol/l (19%) and 0.07 mmol (5.5%) in pravastatin and dietary advice groups, respectively] as high density lipoprotein rose non-significantly by 0.6 mmol/l in both groups. Weight, basal metabolic rate, fasting glucose and triglycerides did not change significantly in either group. CONCLUSIONS: Dietary advice plus pravastatin significantly reduced total cholesterol in HIV-positive individuals taking protease inhibitors, without significant adverse effects. The inclusion of pravastatin substantially increases the magnitude of the change, which is comparable with changes achieved in endogenous hyperlipidaemia.

Anticholesteremic Agents↗
PubMed2001

Effect of computer-assisted self-interviews on reporting of sexual HIV risk behaviours in a general population sample: a methodological experiment.

OBJECTIVES: To develop methods to maximize the accuracy of reporting HIV risk behaviours in a general population survey. We assessed the feasibility of using a computer-assisted self-completion interview (CASI) in comparison with pen-and-paper self-completion interview (PAPI). DESIGN: A probability sample survey of residents aged 16-44 years in Britain, with alternate assignment of addresses to interview by CASI (462) or PAPI (439). METHODS: Personal interviews exploring demographic and sexual behaviour variables. Principal outcome measures were the impact of CASI in relation to PAPI on data quality and rates of reporting a range of behaviours. RESULTS: A total of 901 interviews were completed; 829 individuals were eligible for and accepted the self-completion module. Internal consistency of data items was greater with CASI than PAPI and item non-response was lower. Overall, there was no significant difference in rates of reporting between CASI and PAPI. The main effect for CASI compared with PAPI in a generalized estimating equation (GEE) analysis was an OR (95% CI) of 1.04 (0.92-1.17). Variables were also examined individually, including homosexual partnership (adjusted OR 1.26 95%, CI 0.69-2.29), payment for sex (adjusted OR 0.68 95% CI 0.29-1.59), masturbation (adjusted OR 0.89 95% CI 0.66 1.22) and five or more partners in the past 5 years (OR 0.85 95% CI 0.61 -1.19). CONCLUSION: We found no evidence of a consistent effect of CASI on rates of reporting sexual HIV risk behaviours in this sample. CASI resulted in improvement in internal consistency and a reduction in missed questions.

Adolescent↗
PubMed2001

Does the extract of the plant Echinacea purpurea influence the clinical course of recurrent genital herpes?

An increasing proportion of the population perceive complementary medicine as a safer alternative for non-life threatening conditions such as genital herpes. The extract of the plant Echinacea purpurea (Echinaforce) has been shown to have immunomodulating properties and has been advocated in the lay press for the treatment of genital herpes. This study, a single centre, prospective, double blind, placebo-controlled cross-over trial set out to assess whether an extract of the plant and root of E. purpurea can prevent or decrease the frequency and severity of genital herpes recurrences. These were assessed using a detailed history and clinical review of symptoms. Visual analogue scales were used for documentation and haematological and immunological parameters were measured. Over a one-year period, 50 patients took part in the study receiving 6 months' placebo and 6 months' Echinaforce each. No statistically significant benefit could be detected in this study comparing placebo versus Echinaforce in the treatment of frequently recurrent genital herpes.

Adult↗
PubMed2001

Midwives and HIV antibody testing: identifying the key factors for achieving the targets.

A questionnaire study was designed to assess whether differences in knowledge and attitudes to HIV infection existed between midwives working in areas of higher and lower HIV prevalence, and the extent to which this influenced the uptake of HIV antibody testing by their clients. The response rate was 75% (219/292). Midwives in an area of a higher HIV prevalence had significantly greater experience with HIV-positive mothers, were more confident with HIV-related issues and were less judgemental in their attitudes than midwives in an area of lower HIV prevalence. However, midwives who had been offering HIV testing for more than 2 years were significantly less likely to achieve an HIV antibody test uptake rate of more than 75% than those who had been offering testing for less than 2 years, 35% (95% confidence interval [CI]: 22.2-48.6%) vs 67% (95% CI: 56.3-76.0%), respectively. This demonstrates the need for regular updating of midwives about HIV antibody testing.

Female↗
PubMed2000

Cost effectiveness of expanded antenatal HIV testing in London.

BACKGROUND: Recently the Department of Health announced the introduction in England of voluntary universal HIV screening in early pregnancy to prevent vertical transmission. New data have shown the importance of HIV infection in infants born to mothers who were HIV-negative in early pregnancy and who acquired HIV later in pregnancy or during lactation. This requires consideration of repeat testing in late pregnancy and testing of partners of pregnant women (expanded antenatal HIV testing). OBJECTIVE: To estimate cost effectiveness of expanded antenatal HIV testing in London (England) within the framework of universal voluntary HIV screening in early pregnancy. DESIGN: Incremental cost-effectiveness analysis. METHODS: Cost estimates of service provision for HIV-positive children and adults by stage of HIV infection were combined with estimates of health benefits for infants and parents and with costs of counselling and testing (testing costs). In a pharmacoeconomic model cost effectiveness was estimated for expanded antenatal HIV testing in London for universal and selective strategies. RESULTS: Testing costs in the plausible range of pounds sterling 4 to pounds sterling 40 translate into favourable incremental cost-effectiveness estimates for expanded antenatal HIV testing in London which is already at low numbers of vertical transmissions averted per 100000 pregnant women who test HIV-negative in early pregnancy. Favourable cost effectiveness for universal expanded testing would require testing costs in the lower range, whereas selective expanded testing may produce favourable cost effectiveness at testing costs close to pounds sterling 40. CONCLUSION: Based on pharmaco-economic considerations, the authors believe that implementation of expanded HIV testing in London should be considered.

Adult↗
PubMed2000

Changes in acquired immunodeficiency syndrome-related lymphoma since the introduction of highly active antiretroviral therapy.

Clinical data on 7840 HIV-positive patients, representing 43 745 patient-years of follow-up, has been collected. All patients with ARL since 1986 (n = 150) were assessed at presentation for prognostic factors and outcomes recorded. Comparisons are made between cases in the pre-HAART era (1988-1995), and the HAART era (1996-1999). Statistical models are used to calculate the incidence of ARL and factors predicting its development. The incidence of ARL has not changed over time (3 to 7 of 1000 patients per year, P = .933), but contributes to a greater percentage of first AIDS-defining illnesses (ADI) in the HAART era (P < or = .0001). Older age, nadir CD4 count, and no prior HAART use, predict the development of ARL. There has been no change in stage at presentation, presence of B symptoms, performance status, or marrow involvement between the 2 time cohorts or between patients with or without prior HAART exposure. Similarly, there is no difference in survival duration between the pre-HAART and HAART era (log rank P = .15) or specifically in patients treated with HAART before ARL diagnosis (log rank P = .12). The use of HAART has not yet been shown to influence the incidence or survival of ARL. However, because nadir CD4 count and use of HAART are independent predictors of ARL development, this may translate into a future fall in new cases. (Blood. 2000;96:2730-2734)

Adult↗