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Biomedical subjects

D A Hawkins

Publications and source records attributed to D A Hawkins.

At least 19 recordsLinked to original sources
PubMed2005

Increasing detection of asymptomatic syphilis in HIV patients.

BACKGROUND/OBJECTIVES: The burden of new syphilis diagnoses in London has mainly been in men who have sex with men (MSM), many of whom are co-infected with HIV. Our HIV unit introduced regular serological screening for syphilis during routine follow up care to detect patients who may be at risk of asymptomatic infection. We assessed if this remained an effective and necessary strategy in the second year since introduction. METHODS: All HIV outpatients with newly positive syphilis serology between 1 May 2002 and 30 April 2003 were identified using a prospectively collected database. Only patients who were asymptomatic at the time of screening were included (cohort B). They were compared to patients in the exact preceding year (cohort A). RESULTS: 2655 patients had at least one CD4 count measured in the period (surrogate marker for patients having routine follow up bloods), of whom 2389 (90%) had syphilis serology performed. 40 individuals were found to have early asymptomatic infection (two were re-infections), compared to 26 patients in cohort A. These 40 patients represented 36% of all patients with infectious syphilis treated within our department and 56% of those who were HIV positive. The event rate in cohort B was 7.3 per 1000 patient years (CI 5.2 to 9.9) compared to 2.8 (CI 1.8 to 4.0) in cohort A. CONCLUSION: Routine screening is effective and has detected increasing numbers of HIV outpatients with early asymptomatic syphilis. Our department will continue this strategy for all HIV patients during their follow up care. We recommend that other units adopt similar initiatives that assist with regional control of the UK syphilis epidemic.

Adult↗
PubMed2002

Interaction between saquinavir soft-gel and rifabutin in patients infected with HIV.

AIMS: To evaluate the potential pharmacokinetic interaction between the HIV protease inhibitor saquinavir and rifabutin. METHODS: Fourteen HIV-infected patients provided full steady-state pharmacokinetic profiles following administration of rifabutin alone (300 mg once daily) or saquinavir soft-gel formulation (1200 mg three times daily) plus rifabutin (300 mg once daily) in this open label, partially randomized study. RESULTS: Coadministration of saquinavir and rifabutin resulted in a reduction in saquinavir AUC(0,8 h) and C(max)(0,8 h) of 47% (95% CI 30, 60%) and 39% (95% CI 11, 59%), respectively. Rifabutin AUC(0,24 h) and C(max)(0,24 h) was increased by an average of 44% (95% CI 17, 78%) and 45% (95% CI 14, 85%), respectively. Saquinavir in combination with rifabutin was well tolerated. Gastrointestinal intolerance and asymptomatic increases in liver enzymes were the only adverse events of note. CONCLUSIONS: Administration of rifabutin with saquinavir may decrease the efficacy of this HIV protease inhibitor.

Adult↗
PubMed2001

Postexposure prophylaxis for HIV infection.

Postexposure prophylaxis (PEP) is routinely recommended following occupational exposure to HIV. Most PEP regimens involve the use of 2 nucleoside reverse transcriptase inhibitors with or without the addition of a protease inhibitor. PEP is also increasingly being prescribed following nonoccupational exposure to HIV. It is important that careful risk assessment be performed before prescribing PEP in both the occupational and nonoccupational settings and that risk reduction measures be emphasized.

Animals↗
PubMed2000

Hospital infection control in an era of HIV infection and multi-drug resistant tuberculosis.

Tuberculosis infection control in hospitals has received renewed interest after decades of low prominence following the occurrence of multiply drug-resistant strains in populations of patients with immune systems affected by HIV. This paper examines the history of tuberculosis infection control in hospitals and how recent outbreaks have influenced contemporary measures. The principal infection control measure must always be early recognition and isolation of patients in HIV-care situations who may be dispersing Mycobacterium tuberculosis, in both ward and outpatient areas. If there is either a high degree of suspicion or proven TB, patients should be housed in negative pressure isolation rooms whilst undergoing treatment and investigation. Procedures which may generate infectious aerosols should be carried out in similarly ventilated rooms. The quality assurance in such infection control is through the administrative systems put in place, staff training and the engineering controls of isolation room ventilation.

AIDS-Related Opportunistic Infections↗
PubMed2000

Delavirdine in combination with zidovudine in treatment of human immunodeficiency virus type 1-infected patients: evaluation of efficacy and emergence of viral resistance in a randomized, comparative phase III trial. The M/3331/0013B Study Group.

We compared the activity of delavirdine (DLV) plus zidovudine (AZT) (n = 300) with that of AZT (n = 297) against human immunodeficiency virus type 1 in a randomized, double-blind, placebo-controlled trial. DLV exerted a transient antiviral effect, and mutations for resistance to DLV were found in more than 90% of subjects at week 12. The K103N mutation, which confers nonnucleoside reverse transcriptase inhibitor cross-resistance, was found in 85% of the patients.

Anti-HIV Agents↗
PubMed1999

Pharmacokinetics and hemodynamic effects of single oral doses of thalidomide in asymptomatic human immunodeficiency virus-infected subjects.

Thalidomide (alpha-N-phthalimidoglutarimide), a potent inhibitor of tumor necrosis factor alpha (TNF-alpha), is proving to be a promising drug in the treatment of a number of inflammatory, autoimmune, and HIV-associated disorders. The pharmacokinetics and hemodynamic effects of two single oral doses of thalidomide (100 and 200 mg) were investigated, using a randomized, two-period crossover design, in a group of asymptomatic, male HIV-seropositive subjects. Thalidomide pharmacokinetics were linear at the doses studied, and were best described by a one-compartment model with first-order absorption and elimination processes. The drug was rapidly absorbed, with a mean absorption half-life of 0.95 hr (range, 0.16-2.49 hr) and 1.19 hr (range, 0.33-3.53 hr) after 100- and 200-mg doses, respectively. The corresponding mean Cmax values were 1.15+/-0.24 microg/ml (100 mg) and 1.92+/-0.47 microg/ml (200 mg; p<0.001), which were achieved (Tmax) at 2.5+/-1.5 h and 3.3+/-1.4 hr, respectively. Plasma concentrations of thalidomide declined thereafter, in a log-linear manner, with elimination half-lives of 4.6+/-1.2 hr (100 mg) and 5.3+/-2.2 hr (200 mg). The apparent volumes of distribution (Vdss/F) were 69.9+/-15.6 liters (100 mg) and 82.7+/-34.9 liters (200 mg) while total body clearances (Cl/F) were 10.4+/-2.1 and 10.8+/-1.7 liters/hr, respectively. Significant dose-dependent decreases in supine systolic and diastolic blood pressures were seen for up to 2 hr postdosing; somnolence, headache, dizziness, and confusion were also reported more frequently at the higher dose of thalidomide.

Administration, Oral↗
PubMed1999

Efficacy and safety of combination therapy with delavirdine and zidovudine: a European/Australian phase II trial.

The objective of the study was to investigate the safety and antiviral effect of three delavirdine dose regimens or placebo in combination with zidovudine in patients who were already taking zidovudine. Eighty-nine symptomatic HIV-1 seropositive individuals with CD4 cell counts between 50 and 350 cells/microl were included in this trial The influence of combination therapy on viral susceptibility to both zidovudine and delavirdine was investigated. Death or the occurrence, or re-occurrence of an AIDS-defining illness was considered as a clinical endpoint. The addition of delavirdine to the antiretroviral treatment regimen resulted in a significant, but transient, reduction in virus load, as determined by quantitative RNA measurements. CD4+ cell count did not change significantly. Susceptibility to zidovudine remained unchanged after 12 weeks of combination therapy, while 70% of the patients demonstrated a substantial decrease (> 10-fold) in sensitivity to delavirdine. Two patients suffered from an AIDS-defining disease during the study. No deaths occurred. Generally, the drug appeared to be safe. Skin rash was the most frequently observed adverse event (52%). In most patients the rash either resolved spontaneously or was treated successfully with a short course of antihistamines. The definite place of the compound in the management of HIV disease, in particular when given in combination with other antiretroviral agents, remains to be further explored.

Anti-HIV Agents↗
PubMed1998

Treatment of HIV-related fluconazole-resistant oral candidosis with D0870, a new triazole antifungal.

OBJECTIVES: To evaluate the efficacy and tolerance of D0870 in the treatment of HIV-related fluconazole-resistant oro-oesophageal candidosis. DESIGN: Multicentre open study. PATIENTS: HIV-seropositive patients with oro-oesophageal candidosis despite at least 7 days of treatment with fluconazole at doses of 100 mg per day or more. METHODS: Patients received an initial dose of D0870 (150 mg), then 25 mg per day for 6 days. Symptoms and signs of candidosis were compared at entry and on days 3 and 7 of treatment. At each visit, samples were taken for safety monitoring and for in vitro susceptibility testing of Candida isolates. Limited pharmacokinetic samples were taken on days 1 and 7. RESULTS: Of 26 evaluable patients, 16 showed partial improvement, nine showed no improvement, and only one had full clearance of thrush by day 7. In vitro testing of the cleared patient's isolate suggested that it was susceptible to fluconazole. Symptoms of dysphagia cleared in 14 and improved in five of the 22 patients with presumptive oesophageal involvement at entry. Pharmacokinetic measurement showed wide variability in maximum D0870 levels recorded on day 1 (range, 0.07-0.34 mg/l) and susceptibility testing of isolates also showed a range of minimal inhibitory concentration values to D0870 (range, < 0.06-8 mg/l; median, 0.25 mg/l). When these data were combined with clinical response there was a strong suggestion that lack of symptomatic improvement was related to low plasma D0870 levels or to the presence of less D0870-susceptible isolates. Six patients were noted to have a fall in haemoglobin, three of whom were receiving concomitant therapy known to suppress bone marrow. Three patients reported headaches as adverse events that were attributed to study medication, but D0870 was well tolerated overall. CONCLUSIONS: D0870 shows promise in the treatment of fluconazole-resistant oro-oesophageal candidosis and was well tolerated, although efficacy in this difficult-to-treat patient group was probably limited due to the inadequate plasma levels achieved in this pilot study with the low doses of D0870 administered.

AIDS-Related Opportunistic Infections↗
PubMed1997

A double-blind placebo-controlled phase II trial of thalidomide in asymptomatic HIV-positive patients: clinical tolerance and effect on activation markers and cytokines.

A randomized double-blind, placebo-controlled study was performed to determine the safety, efficacy, and effect of thalidomide on a variety of immunological and biochemical parameters in asymptomatic human immunodeficiency virus (HIV)-positive patients. Nineteen male patients with elevated markers of immune activation and CD4 cell counts above 400/mm3 were randomized to either placebo or thalidomide at 100 mg/day for 24 weeks. However, only 3 (of 10) patients receiving thalidomide completed all 24 weeks compared to 6 (of 9) patients receiving placebo. This was mainly due to fatigue (somnolence is a recognized side effect), although this was also seen to a lesser extent in the placebo group and so may not be drug attributable. No significant changes in CD4/CD8 count, activation markers, TNF-alpha, or TNFR1 were observed. However, a nonsignificant trend toward inhibition of mitogen-induced TNF-alpha production was observed in the thalidomide arm. The lack of systemic effect and the lower tolerance of thalidomide (at this dose) in asymptomatic patients highlights the need for pharmacokinetic analysis to address possible absorption problems and the need for more potent and less toxic TNF-alpha inhibitors to be developed for use in this type of study.

Adult↗