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Biomedical subjects

B G Gazzard

Publications and source records attributed to B G Gazzard.

At least 37 records · Page 2Linked to original sources
PubMed2001

Cessation of secondary prophylaxis in patients with cryptococcosis.

Cryptococcal disease in HIV-positive individuals is usually a consequence of advanced immunosuppression. Treatment consists of long period of induction therapy followed by long-term secondary prophylaxis, usually with fluconazole. The introduction of highly active antiretroviral therapy has resulted in improvements in immunological function such that the cessation of primary and secondary prophylaxis against several opportunistic infections has become possible. We report our experience of the cessation of secondary antifungal prophylaxis in patients responding to highly active antiretroviral therapy.

AIDS-Related Opportunistic Infections↗
PubMed2001

Etiology and natural history of neutropenia in human immunodeficiency virus disease: a prospective study.

The objective of this prospective, observational study was to define the natural history of neutropenia in human immunodeficiency virus (HIV) disease. Eighty-seven consecutive patients developing neutropenia (absolute neutrophil count [ANC], <1000 cells/mm(3)) were recruited and closely followed for the duration of the episode. Episodes lasted a median of 13 days, with a mean ANC nadir of 660 cells/mm(3). Presumed or proven infection occurred in 12 (17%) of 71 evaluable subjects, and culture-proven infection occurred only in 6 (8%) of 71. Most of the episodes of neutropenia were brief, mild to moderate in nadir, and self-limiting without complications. Myelosuppressive therapies were implicated in almost all episodes. Serious infections occurred infrequently and were associated with low ANC nadirs but not with duration of the neutropenic episode. Low CD4(+) cell counts also increased the risk of infection complicating an episode of neutropenia.

Adult↗
PubMed2001

PCR-ELISA: a new simplified tool for tracing the source of cryptosporidiosis in HIV-positive patients.

Cryptosporidium parvum is a major parasitic cause of death in end-stage AIDS patients that results from both zoonotic and person-to-person transmission. Recent studies have provided evidence that parasites causing zoonotic disease and those causing anthroponotic infection are genetically distinct. Isolates carrying "animal"-type genetic markers were presumed to be the result of zoonotic spread, either directly or through contaminated food and water. The need for a genotype-specific diagnostic tool that can provide clues as to the origin and possible modes of spread of C. parvum strains has been recognised. Here, we report the development of such a tool for C. parvum based on polymerase chain reaction-enzyme linked immunosorbent assay that enables the accurate typing of isolates from HIV-seropositive and HIV-negative patients presenting with diarrhoea from the United Kingdom and Canada. This study also showed that zoonotic transmission might be predominant in the HIV-positive patient group in the United Kingdom.

AIDS-Related Opportunistic Infections↗
PubMed2001

Effect of octreotide on small intestinal motility in HIV-infected patients with chronic refractory diarrhea.

Octreotide has been used to treat HIV-associated diarrhea. We aimed to assess the effect of octreotide on small intestinal motility in a group of HIV infected individuals with chronic diarrhea. Small intestinal motility was measured continuously for 48 hr by ambulatory strain gauge manometry in 12 HIV seropositive subjects with chronic diarrhea. During the second 24-hr period, intravenous octreotide was administered (100 microg every 8 hr). Postprandial and nocturnal fasting motility data were compared before and during administration of octreotide. Octreotide was associated with increased numbers of migrating motor complexes (MMCs) (7.25 vs 4.92, P = 0.03), and a relative decrease in the duration of phase II (22% vs 49.8, P = 0.03) during nocturnal fasting activity. Postprandial activity was absent in half of the subjects and the duration significantly reduced in the remainder. In conclusion, octreotide has a significant effect on small intestinal motility in HIV-infected individuals with diarrhea, which may influence intestinal transit.

Adult↗
PubMed2001

The changing pattern of AIDS-defining illnesses with the introduction of highly active antiretroviral therapy (HAART)in a London clinic.

OBJECTIVES: To quantify the progressive impact of combination antiretroviral therapy (ART) on the incidence of AIDS-defining illnesses (ADIs) over a 9-year period. METHODS: Retrospective cohort study. Eligible patients were 1538 AIDS-free, HIV-1-positive patients attending a large HIV clinic in west London who were at risk of developing AIDS because their CD4 count had declined to < or =350 x 10(6)/l cells during the period 1 January 1990 and 31 December 1998. Incidence rates for the 12 most frequent ADIs were compared for two time periods, 1990-1995 (pre-HAART) and 1996-1998 (post-HAART), using Poisson regression methods. Multivariate Poisson regression models were used to examine the contribution of ART and HAART to any observed temporal trends in incidence rates. RESULTS: After a median follow-up of 35 months, 450 (29%) patients had developed AIDS. Between the two time periods there was a significant decrease in the incidence of Pneumocystis carinii pneumonia (PCP) by 35% (4.11 per 100 person-years in 1990-1995 vs. 2.67 in 1996-1998;P= 0.007), Kaposi's sarcoma by 34% (3.27 vs. 2.17;P= 0.022) and cryptosporidiosis by 60% (0.76 vs. 0.31;P= 0.029). A non-significant reduction in incidence was observed for cryptococcosis by 45% (0.81 vs. 0.45;P= 0.11), oesophageal candidiasis by 29% (3.34 vs. 2.39;P= 0.053) and mycobacterium avium complex by 18% (1.58 vs. 1.29;P= 0.4), and a non-significant increase was observed for tuberculosis by 17% (0.62 vs. 0.73;P= 0.66) and non-Hodgkins lymphoma (NHL) by 51% (0.43 vs. 0.65;P= 0.31). The incidence of cerebral toxoplasmosis, cytomegalovirus, recurrent bacterial chest infections and dementia remained stable. There was a clear stepwise reduction in the incidence of PCP, Kaposi's sarcoma and cryptosporidiosis with the use of non-H AART and HAART regimens relative to no ART. In a multivariate analysis, the use of ART and HAART explained the progressive decrease in incidence of PCP and Kaposi's sarcoma. CONCLUSIONS: The incidence of most ADIs has decreased over the last 9 years. The striking reduction in the inci-dence of PCP and Kaposi's sarcoma since 1996 can be attributed to the use of combination ART and particularly HAART. The non-significant increase in the incidence of NHL and tuberculosis needs confirmation in other patient cohorts.

AIDS-Related Opportunistic Infections↗
PubMed2001

Reasons for non-adherence to antiretroviral therapy: patients' perspectives provide evidence of multiple causes.

The objective of the study was to define common reasons for non-adherence (NA) to highly active antiretroviral therapy (HAART) and the number of reasons reported by non-adherent individuals. A confidential questionnaire was administered to HIV-seropositive patients taking proteinase inhibitor based HAART. Median self-reported adherence was 95% (n = 178, range = 60-100%). The most frequent reasons for at least 'sometimes' missing a dose were eating a meal at the wrong time (38.2%), oversleeping (36.3%), forgetting (35.0%) and being in a social situation (30.5%). The mean number of reasons occurring at least 'sometimes' was 3.2; 20% of patients gave six or more reasons; those reporting the lowest adherence reported a significantly greater numbers of reasons (rho = - 0.59; p < 0.001). Three factors were derived from the data by principal component analysis reflecting 'negative experiences of HAART', 'having a low priority for taking medication' and 'unintentionally missing doses', accounting for 53.8% of the variance. On multivariate analysis only the latter two factors were significantly related to NA (odds ratios 0.845 and 0.849, respectively). There was a wide spectrum of reasons for NA in our population. The number of reasons in an individual increased as adherence became less. A variety of modalities individualized for each patient are required to support patients with the lowest adherence.

Acquired Immunodeficiency Syndrome↗
PubMed2001

A phase I/II study of the safety and activity of a microsphere formulation of KNI-272 in patients with HIV-1 infection.

Eighteen patients with symptomatic HIV disease were enrolled into a phase I/II study of a microsphere formulation of the HIV protease inhibitor KNI-272, with doses escalated up to a maximum dose of 60 mg/kg/day. One patient developed reversible elevation in hepatic transaminase. The plasma half-life of the drug was very short, varying between 0.25 and 1.1 h. No consistent effect on plasma HIV RNA levels or CD4(+) lymphocyte counts was seen.

Adult↗
PubMed2001

Distribution of K103N and/or Y181C HIV-1 mutations by exposure to zidovudine and non-nucleoside reverse transcriptase inhibitors.

Our aim was to identify whether zidovudine has a role in the emergence of the K103N resistance mutation in the HIV-1 reverse transcriptase gene on non-nucleoside reverse transcriptase inhibitors (NNRTIs). No difference was found in the exposure to zidovudine or major zidovudine mutations between the resistance patterns K103N-/Y181C+, K103N+/Y181C- and K103N+/ Y181C+, either in group A (patients on nevirapine and previously NNRTI naive) or in group B (on any NNRTI and experience of two or more NNRTIs including nevirapine). Group B patients had the highest prevalence of K103N+/Y181C+. In conclusion, zidovudine seems not to determine the emergence of K103N; however, there appears to be an accumulation of NNRTI resistance mutations with sequential use of NNRTIs.

Anti-HIV Agents↗
PubMed2001

Incidence and risk factors for the development of indinavir-associated renal complications.

OBJECTIVES: To describe the incidence and risk factors for the development of indinavir-associated renal complications (IRC), and subsequent clinical outcome. PATIENTS AND METHODS: This was a retrospective cohort study based on two large HIV centres in London. Eligible patients received indinavir for at least 1 week between 1 December 1995 and 28 February 1999. Development of IRC was ascertained by case-note review. Multivariate logistic regression and Cox Proportional Hazard's model analysis were used to determine independent risk factors for the development of IRC. RESULTS: 781 patients were eligible. Median CD4 count and viral load at indinavir initiation were 117 x 10(6) cells/L and 47 332 copies/mL, respectively. Median indinavir exposure was 53 weeks (IQR: 20-83). Many patients received other potentially nephrotoxic drugs during indinavir treatment: co-trimoxazole (46%), aciclovir (33%) or both (20%). Overall IRC incidence was 7.3% (6.7 per 100 person-years indinavir exposure). Cases presented with loin pain (58%), renal colic (42%) or dysuria (19%). Identified precipitating events (26%) included fluid depletion or altered indinavir regimen. In the majority of cases indinavir therapy was continued and there was no progressive rise in creatinine levels. In the multivariate analysis, for indinavir treatment >74 weeks there was a reduced risk of developing IRC (OR = 0.23, 95% CI 0.09-0.57, P = 0.001). Concomitant aciclovir increased the IRC risk (OR = 1.99, 95% CI 1.14-3.51, P = 0.016). Factors not associated with outcome were age, gender, ethnicity, baseline CD4 count and viral load, concomitant co-trimoxazole, or use of specific antiretrovirals. CONCLUSION: An overall IRC incidence of 7.3% was identified. Concomitant aciclovir doubled the risk of IRC and we therefore recommend careful monitoring when prescribing aciclovir with indinavir. A precipitating event was identified in 26% of IRC cases, many of which could have been avoided.

Adult↗
PubMed2001

The potential place of tenofovir in antiretroviral treatment regimens.

Advice from the Food & Drug Administration and the European Medicines Commission indicates that tenofovir is likely to be licensed shortly for use in patients failing antiretroviral therapy as part of a regimen constructed by the clinician. Tenofovir is a nucleotide (NtRTI) that acts in a similar way to nucleoside analogues by inhibiting reverse transcriptase, producing similar HIV plasma viral load fall. In use up to 48 weeks it appears to be safe without evident toxicity. It has particular value because it has activity against many HIV viruses with mutations which render them insensitive to other nucleoside analogues. Its eventual optimal role in treatment, particularly whether it should be part of a first line regimen, awaits the outcome of further studies.

Adenine↗
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↗
PubMed2000

Eradication of cryptosporidia and microsporidia following successful antiretroviral therapy.

OBJECTIVES: Incidence of opportunistic protozoal infections causing diarrheal illnesses in patients with HIV has decreased since the introduction of highly active antiretroviral therapy (HAART). The objective of this study was to determine whether the parasites, cryptosporidia, and microsporidia were effectively eradicated or only suppressed following treatment. DESIGN: Six HIV-positive patients with diarrheal symptoms caused by cryptosporidia or microsporidia were prospectively followed up with stool samples and duodenal biopsies. Samples were taken before HAART, between 1 to 3 months, and 6 months post-HAART. METHODS: Duodenal samples were analyzed using routine histology and transmission electron microscopy. Stool samples were analyzed by both light microscopy and polymerase chain reaction (PCR) techniques. RESULTS: Patients who responded successfully to HAART eradicated both cryptosporidial and microsporidial organisms. Symptoms improved within 1 month of therapy but complete eradication of the organisms was only observed after 6 months of treatment. CONCLUSIONS: AIDs-related cryptosporidiosis and microsporidiosis can be cured following successful antiretroviral therapy.

AIDS-Related Opportunistic Infections↗
PubMed2000

Absence of association between individual thymidine analogues or nonnucleoside analogues and lipid abnormalities in HIV-1-infected persons on initial therapy.

Changes in levels of triglycerides and cholesterol during antiretroviral therapy raise concerns regarding an increased future risk of atherogenic disease and may precede the appearance of fat redistribution. Hypotheses regarding the impact of nucleoside analogues on adipocytes provide a possible explanation for metabolic and clinical fat disturbances. It is unclear whether the choice of nucleoside analogue combination or coadministration of nonnucleoside agents influences change in lipids. We performed a cross-sectional analysis of 135 persons receiving their first nucleoside analogue plus nonnucleoside-based combination antiretroviral regimen for at least 1 month and for whom cholesterol and triglyceride values were available on therapy. Univariate and multivariate regression models were used to explore the relation between cholesterol and triglycerides, as continuous variables with other variables. Both significant and nonsignificant variables from univariate analyses were evaluated in multivariate models to limit possible confounders. No association with drug choice was observed, either when comparing thymidine analogues (stavudine or zidovudine), all nucleoside analogue combinations or choice of either efavirenz or nevirapine as nonnucleoside. Age and triglyceride levels were found in a multivariate analysis to be associated with higher cholesterol. Only higher cholesterol was associated with higher triglyceride levels. In conclusion, no differences were observed between choice of drug or combination on cholesterol or triglyceride values during therapy. Older individuals may be more likely to have elevated cholesterol values.

Adult↗
PubMed2000

Cardiac autonomic dysfunction in AIDS is not secondary to heart failure.

OBJECTIVE: Heart rate variability (HRV) is a marker of cardiovascular autonomic tone, and is also known to be reduced in association with cardiac dysfunction. Abnormal autonomic function tests are common in HIV infected individuals, but the contribution of heart disease to such findings is not known. Spectral analysis of heart rate variability is a sensitive technique for measurement of cardiovascular autonomic function, which also allows differential assessment of parasympathetic and sympathetic components. The aim of this study was to characterise the nature of autonomic dysfunction in patients with AIDS and to compare our findings with those seen in HIV seronegative patients with established heart disease. METHODS: HRV was measured prospectively by spectral analysis in 10 subjects with dilated cardiomyopathy (age 45.7+/-6.9 years), 10 subjects with AIDS and no clinical evidence of heart disease (age 37.9+/-5.4 years), and 10 healthy HIV seronegative controls (age 41.7+/-13.9 years). RESULTS: All components of HRV were reduced in subjects with cardiomyopathy (P<0.005), and markedly so in subjects with AIDS (P<0. 0001) compared with controls. CONCLUSIONS: HIV infection may be associated with severe global autonomic dysfunction, which is not related to heart disease.

Acquired Immunodeficiency Syndrome↗