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Biomedical subjects

Jan M Prins

Publications and source records attributed to Jan M Prins.

11 recordsLinked to original sources
PubMed2003

Dynamics of the pool of infected resting CD4 HLA-DR- T lymphocytes in patients who started a triple class five-drug antiretroviral regimen during primary HIV-1 infection.

Starting standard antiretroviral therapy within 10 days after the onset of a primary HIV-1 infection cannot prevent the establishment of a reservoir of HIV-1-infected memory CD4 T cells. Here we studied the reservoir of HIV-1-infected memory CD4 T cells in four patients who started a triple class, five-drug regimen during primary HIV-1 infection. There was a strong correlation between the proportion of productively infected CD4 HLA-DR- T lymphocytes and plasma HIV-1 RNA levels (r=0.852; P<0.001) during the first 24 weeks of therapy. Within 45 weeks of treatment, in three of the four patients the proportion of productively infected CD4 HLA-DR- T lymphocytes was reduced below the level of quantification. In the fourth patient the cellular reservoir remained quantifiable. In two patients who stopped therapy 44 weeks after initiation an immediate rebound of the plasma HIV-1 RNA level and the proportion of productively infected CD4 HLA-DR- T lymphocytes occurred. In conclusion, initiation of a potent five-drug, triple class regimen during primary HIV-1 infection does not result in virus-specific immune control upon discontinuation of therapy after 44 weeks. Therefore, longer or even stronger suppression of viral replication might be necessary to achieve this goal in primary HIV-1 infection.

Anti-HIV Agents↗
PubMed2002

Health-related quality of life and posttraumatic stress disorder among survivors of an outbreak of Legionnaires disease.

A follow-up study of 122 survivors of an outbreak of legionnaires disease (LD) in The Netherlands was conducted to determine persistence of symptoms, health-related quality of life (HRQL), and presence of posttraumatic stress disorder (PTSD). Seventeen months after diagnosis of LD, survivors completed a questionnaire assessing symptoms and HRQL and a questionnaire assessing PTSD. The most prevalent new symptoms were fatigue (in 75% of patients), neurologic symptoms (in 66%), and neuromuscular symptoms (in 63%). HRQL was impaired in 7 of the 8 dimensions assessed by the HRQL questionnaire, and 15% of patients experienced PTSD. Symptoms and impaired HRQL persisted for >1.5 years. As a result of the design of this study, it could not be inferred whether Legionella pneumophila infection, severe pneumonia in general, or the outbreak situation was responsible for impaired well-being. However, awareness of this problem by health care providers may improve the aftercare of patients.

Adult↗
PubMed2002

Improved long-term suppression of HIV-1 replication with a triple-class multidrug regimen compared with standard of care antiretroviral therapy.

BACKGROUND: The treatment of HIV-1-infected patients with triple-drug combination therapy results in profound suppression of viral replication. In most therapy-naive patients plasma HIV-1-RNA levels (pVL) drop below the lower limit of quantification (LLQ) of currently used assays. In a large percentage of such patients, more sensitive assays provide evidence of residual viral replication. The question is whether more potent therapy can further suppress this residual replication. METHODS: Thirty control patients who, using very strict criteria, had not experienced virological failure during 3 years of standard therapy, were compared with 10 patients treated with a five-drug regimen, consisting of three different classes of antiretroviral drugs (alternative multidrug regimen). A modified ultrasensitive assay with an LLQ of 5 copies/ml was used to re-test plasma obtained at week 48 and at three timepoints at and around week 144. RESULTS: At weeks 48 and 144 pVL could be quantified significantly more frequently in control patients than in patients using the alternative multidrug regimen (week 48: 42 versus 0% with quantifiable pVL, P = 0.017; week 144: 60 versus 14% with at least one quantifiable pVL, P = 0.036, respectively). A low baseline CD4T cell count was predictive of quantifiable pVL in control patients, but not in alternative multidrug patients. CONCLUSION: This proof-of-principle study demonstrates that the use of an alternative multidrug regimen results in stronger long-term suppression of pVL compared with clinically successful treatment with standard therapy.

Adult↗
PubMed2002

Duration of antibiotic therapy for cholangitis after successful endoscopic drainage of the biliary tract.

BACKGROUND: Drainage of the obstructed biliary tree is the mainstay of therapy for patients with acute cholangitis; antibiotic therapy is complementary. It is unknown whether it is necessary to continue therapy with antibiotics once biliary drainage is achieved and signs of systemic inflammation have subsided. METHODS: Patients who presented with acute cholangitis and were successfully treated at ERCP were studied retrospectively. Patients were followed for 6 months after ERCP. RESULTS: Eighty patients fulfilled study criteria. In 46% of patients blood cultures grew microorganisms. All patients recovered from the episode under study. Antibiotic therapy after ERCP was given for a median duration of 3 days (range: 0-42). Forty-one patients received antibiotic therapy for 3 days or less, 19 for 4 or 5 days, and 20 patients longer than 5 days. The 3 groups were well-matched. In none of the patients did the index episode of cholangitis result in a secondary complication not present at the time of ERCP. The percentage of patients with recurrent cholangitis (24%) was not statistically different for the 3 groups (p = 0.80). CONCLUSIONS: Short-duration antibiotic therapy (3 days) appears sufficient when adequate drainage is achieved and fever is abating.

Acute Disease↗
PubMed2002

Cryptococcal breast abscess.

A cryptococcal abscess of the breast is uncommon and may mimic a neoplastic lesion. We describe a patient with an isolated cryptococcal infection of the breast, which was treated with oral fluconazole in combination with surgical excision. With the exception of diabetes mellitus type II, no underlying predisposing illness was identified.

Abscess↗
PubMed2002

Stable concentrations of zidovudine, stavudine, lamivudine, abacavir, and nevirapine in serum and cerebrospinal fluid during 2 years of therapy.

For a number of antiretroviral drugs, prolonged suppression of viral replication is related to drug exposure. Therefore, it is important to maintain stable concentrations during prolonged therapy. While studies suggest that saquinavir concentrations decrease over time, we show that concentrations of zidovudine, stavudine, lamivudine, abacavir, and nevirapine in serum and cerebrospinal fluid are stable during 2 years of therapy.

Adult↗
PubMed2002

Legionnaires' disease at a Dutch flower show: prognostic factors and impact of therapy.

After a large outbreak of Legionnaires' disease in the Netherlands, we determined risk factors for intensive care unit (ICU) admission and death and the impact of adequate therapy on ICU-free survival among 141 hospitalized patients. Overall mortality rate was 13%, and ICU mortality rate was 36%. Smoking, temperature >38.5 degrees C, and bilateral infiltrates shown on chest x-ray were independent risk factors for ICU admission or death (all p<0.05). Starting adequate therapy within 24 hours after admission resulted in a higher ICU-free survival rate compared to therapy initiation after 24 hours: 78% versus 54%, respectively (p=0.005). However, delay in providing therapy to patients with urinary antigen tests with negative results did not influence outcome. These data suggest that by using the urinary antigen test on admission a more tailored approach to patients with community-acquired pneumonia may be applied.

Aged↗
PubMed2002

Persistence of viral HLA-DR- CD4 T-cell reservoir during prolonged treatment of HIV-1 infection with a five-drug regimen.

During sustained suppression of plasma viraemia using a standard triple-drug regimen, replication-competent HIV-1 can still be recovered from resting memory CD4 T cells. In an attempt to accelerate the clearance of this pool of infected CD4 T cells, eight antiretroviral therapy-naive HIV-1-infected patients were treated with a five-drug regimen. While plasma HIV-1 RNA levels generally remained below the level of detection (< 5 copies/ml), replication competent HIV-1 was isolated from HLA-DR- CD4 T cells from all patients on multiple occasions throughout treatment. Decay slopes of infected CD4 T cells ranged from -0.061/week (half-life=2.6 months) to +0.003/week (half-life = infinite). Virus was still detectable at the last time point analysed (80-173 weeks) in all patients. Although more intensive treatment results in improved suppression of plasma viraemia compared with standard drug regimens, it does not result in clearance of the viral reservoir in this timeframe. Strategies other than treatment with a combination of five of the currently available drugs need to be pursued in order to achieve eradication of HIV-1 from this cellular reservoir.

Acquired Immunodeficiency Syndrome↗