[A paradox: sarcoidosis in an HIV-positive patient]. / Een paradox: sarcoïdose bij een hiv-positieve patiënt.

BACKGROUND: In view of the diminished number of CD4+ lymphocytes, the co-existence of an HIV infection and sarcoidosis seems paradoxical. Immune reconstitution inflammatory syndrome (IRIS) may be observed in response to anti-retroviral therapy (ART). According to the conventional definition, this is caused by an overwhelming immune response to an already present or to a new agent. CASE DESCRIPTION: We describe the case of a 47-year-old HIV-positive patient, who presented with an exacerbation of his sarcoidosis nine months after initiation of ART. Based on the time course and the dynamics of the CD4+ lymphocyte count, this presentation of disease can be placed in the context of IRIS. CONCLUSION: The presentation or exacerbation of sarcoidosis after initiation of antiretroviral therapy in HIV-positive patients with a low CD4+ count at start of therapy can be placed in the context of IRIS.

[Rhabdomyolysis in a bodybuilder using steroids]. / Rabdomyolyse bij een bodybuilder na gebruik van diverse dopingmiddelen.

A 34-year-old bodybuilder presented at the emergency room with fever, vomiting and muscle cramps that had started during a bodybuilding session. Several days before he started training he had used tablets and intramuscular injections containing the anabolic steroids: dehydro-chloro-methyltestosterone, boldenone and trenbolone. In addition, he had taken clenbuterol tablets, liothyronine tablets and subcutaneous injections of phosphatidylcholine. Laboratory investigations revealed massive rhabdomyolysis. The patient was treated with intravenous fluid replacement and sodium bicarbonate to alkalinize the urine. He recovered quickly and his renal function remained unaffected. 'Doping' among amateur athletes in the Netherlands occurs frequently. Apart from long term side-effects, doping can also cause acute health problems. Therefore it is important to ask about doping use during history taking in amateur athletes.

The risk of needle stick accidents during surgical procedures: HIV-1 viral load in blood and bone marrow.

Health-care workers are at risk to acquire HIV through occupational exposure to blood of HIV-infected patients. The mean risk after a percutaneous exposure is approximately 0.3%. A large inoculum and a source patient with a high plasma viral load increases the transmission risk. To ensure the safety of the operating team, we try to reduce HIV viral load in plasma prior to high-risk interventions (cardiothoracic and orthopaedic surgery). However, in 15.7% of the exposures occurring in the operating room, the possible source material is bone marrow. To make more accurate exposure risk assessments, we measured HIV-1 RNA in both plasma and bone marrow of five HIV-infected patients undergoing surgery. We found that the plasma viral load was not different from the viral load in bone marrow.

Transesophageal echocardiography-guided transvenous biopsy of an intracardiac tumor.

Transesophageal echocardiography with simultaneous fluoroscopic guidance during a transvenous biopsy of an intracardiac tumor is a valuable technique. We present the case of a 67-year-old man with a metastasis in the right atrium from which histological examination of the tumor was indicated. The inaccessible location of the primary tumor in the liver and impaired hemostasis due to cirrhosis necessitated a transvenous biopsy of the metastasis. The procedure and the associated techniques are discussed in this case.

An unusual presentation and way to diagnose hepatocellular carcinoma.

A 67-year-old man with a history of chronic obstructive pulmonary disease (COPD) was admitted with acute progression of dyspnoea, productive cough, fever, elevated central venous pressure, oedema and liver enzyme abnormalities. Pneumonia with secondary right-sided congestive heart failure was considered. Additional abdominal ultrasound examination confirmed by a CT scan showed a mass in the inferior vena cava (VCI) extending into the right atrium. The central liver location and impaired haemostasis rendered liver biopsy impossible. An alternative approach was discussed and guided by two-dimensional transoesophageal electrocardiography accessing the right internal jugular vein, biopsies were taken from the atrial mass with histology suggesting the presence of a hepatocellular carcinoma as the cause of acute dyspnoea.

Differential CD4 T-cell response in HIV-1-infected patients using protease inhibitor-based or nevirapine-based highly active antiretroviral therapy.

OBJECTIVES: To study the dynamics of CD4 T-lymphocyte counts (CD4 counts) after the initiation of either protease inhibitor (PI)-based or nevirapine (NVP)-based first-line highly active antiretroviral therapy (HAART). DESIGN AND METHODS: A retrospective cohort study of 1029 HIV-infected antiretroviral therapy-naive patients initiating either PI-based or NVP-based HAART was carried out. Patients were censored as soon as they experienced virological failure, or changed their original antiretroviral regimen for any reason. RESULTS: In total, 920 and 109 patients initiated PI- and NVP-based HAART, respectively. The patients in the PI group more often had AIDS (15 vs. 6% in the NVP group), had a lower median baseline CD4 count (234 vs. 250 cells/microL in the NVP group) and had higher median baseline plasma HIV-1 RNA levels (pVL) (5.0 vs. 4.7 log10 HIV-1 RNA copies/mL in the NVP group). After 96 weeks of follow-up, the mean increase from baseline in CD4 count, adjusted for baseline CD4 count, age, gender and baseline pVL, was 310 cells/microL in the PI group and 212 cells/microL in the NVP group (P=0.003). This difference was mainly attributable to the patients in the NVP group initiating HAART with a baseline CD4 count below 200 cells/microL. There were no differences between the PI and NVP groups with respect to the change in the number of CD4 cells as a proportion of the total number of lymphocytes. CONCLUSION: Patients successfully treated with NVP-based HAART have a smaller increase in absolute CD4 cells compared with those treated with PI-based HAART.

Change to abacavir-lamivudine-tenofovir combination treatment in patients with HIV-1 who had complete virological suppression.

Patients who have not received previous antiretroviral treatment (ART) have a high failure rate on the combination treatment of abacavir, lamivudine, and tenovir. We assessed the virological failure rate in eight patients with HIV-1 who switched to this combination after having complete virological suppression from their previous long-term ART (median 8.0 months, range 7.5-18.0). Five of the eight patients showed virological failure. Four of these five patients had either the K65R mutation, the M184V/I mutation, or both. This combination of drugs cannot therefore be recommended as alternative treatment in patients with HIV-1 who are fully virologically suppressed.

Evaluation of the rapid immunoassay determine HIV 1/2 for detection of antibodies to human immunodeficiency virus types 1 and 2.

We evaluated the reliability of a rapid human immunodeficiency virus type 1 test for quick clinical decision making, such as in needle-stick accidents. The test was evaluated with 1,160 patients. It proved to be a simple and useful test with 99.6% specificity and 99.4% sensitivity. One patient with late-stage AIDS had a false-negative result.

[Drug-related problems in an emergency department in the center of Amsterdam, June-November 2000]. / Drugsgerelateerde problemen op een afdeling Spoedeisende Hulp in het centrum van Amsterdam, juni-november 2000.

OBJECTIVE: To gain insight into the nature and magnitude of drug-related problems in the emergency department (ED) of a hospital (Onze Lieve Vrouwe Gasthuis) in Amsterdam, the Netherlands. DESIGN: Prospective, observational. METHOD: During the period from June through to November 2000, the following data were recorded for all patients visiting the ED with drug-related problems: age, sex, nationality, form of presentation, presenting complaint, drugs used, diagnostics performed, treatment in the ED and clinical course leaving the ED. RESULTS: During the study period, 214 (1%) patients were seen with drug-related problems. The largest group consisted mainly of young, foreign occasional users of soft drugs (117 patients, 55%). Their complaints were aspecific and harmless. The need for additional diagnostics was limited, with no additional diagnostic tests being carried out in 178 patients (83%). Treatment consisted of reassurance (50 patients, 23%), observation (123 patients, 58%) and medication (85 patients, 40%). Nineteen patients (9%) needed additional treatment (suturing, plastering, etc.). Ten patients (5%) were admitted to the hospital. Reasons for admission were psychotic episodes, prolonged unconsciousness or respiratory problems. CONCLUSION: The magnitude of the drug problem in an emergency department in the centre of Amsterdam and the use of medical resources were limited. The nature of the problem consisted mainly of mild symptoms following the use of soft drugs, usually by young, foreign occasional users.

[Safety regarding invasive procedures in HIV-positive patients]. / Veiligheid rond invasieve ingrepen bij HIV-geïnfecteerde patiënten.

A 46-year-old man and a 58-year-old man, both known for several years with HIV infection, were admitted for operations due to aortic valve insufficiency (aortic valve replacement) and posttraumatic coxarthrosis (total hip replacement) respectively. In accordance with the protocol, preoperative viral infections (HIV, hepatitis B and C) were inventoried, the HIV viral load was lowered medicinally and the operation team informed. During each operation a consultant was present in the operating theatre to provide advice in the case of a needlestick or cut accident. No accidents occurred. Both patients were discharged to home in a good condition.

[Reducing the risk of blood-transmitted infections of HIV, hepatitis B or C virus in a teaching hospital in Amsterdam--evaluation of a protocol for needlestick accidents among hospital staff during the period 1997-2001]. / Risicoreductie van bloedoverdraagbare besmetting met HIV, hepatitis-B- of -C-virus in een opleidingsziekenhuis in Amsterdam--evaluatie van een protocol voor 'prikaccidenten' bij ziekenhuismedewerkers, 1997-2001.

OBJECTIVE: To evaluate a protocol for hospital staff aimed at reducing their risk of exposure to blood-transmitted infections. DESIGN: Prospective. METHOD: In August 1997 a protocol was introduced to the Onze Lieve Vrouwe Gasthuis Hospital in Amsterdam, with procedures to be followed after percutaneous or mucocutaneous blood contact in which there was a chance of transmission of hepatitis B (HBV) or C (HCV), as well as guidelines for the prescription of post-exposure prophylaxis (PEP) after accidents with an HIV risk. In the period 1 August 1997-30 June 2001 data were collected from registration forms that reported accidents and the ensuing events. RESULTS: A total of 403 accidents were reported by 138 (34.2%) physicians, 135 (33.5%) ward nurses, 46 (11.4%) operation assistants, 30 (7.4%) co-assistants, 21 (5.2%) analysts and 33 (8.2%) persons with another position. There was a constant increase in the number of reports over the period. The seroprevalence of the source patients was: 6.9% (25/360) HIV, 8.1% (6/74) HBV and 6.3% (23/363) HCV. PEP was prescribed on 46 occasions: 15 times for an HIV positive source and 31 times for what was initially an unknown HIV source. Following the introduction of a rapid HIV test in September 1999, there was a reduction in the number of unnecessary PEP prescriptions from 4 in 1997, 7 in 1998 and 16 in 1999 to 3 in 2000 and 1 in 2001. All 15 persons who were correctly started on a PEP treatment took the medication for a period of 28 days despite many side effects. No seroconversions were established during the follow-up period of 6 months.

Hyperlactataemia in HIV-infected patients: the role of NRTI-treatment.

BACKGROUND: Long-term treatment with nucleoside reverse transcriptase inhibitors (NRTIs) can induce mitochondrial dysfunction, most severely represented by lactic acidosis. Diagnostic tests for mitochondrial dysfunction are lacking, although persistently elevated serum lactate might be a surrogate marker. OBJECTIVES: To determine the occurrence of hyperlactataemia in HIV-infected patients on NRTI-treatment and to evaluate the possible risk factors. METHODS: Cross-sectional analysis of lactic-acid levels in asymptomatic HIV-infected patients. Hyperlactactaemia was considered mild if between 2.0-5 mmol/l, serious if >5 mmol/l and lactic acidosis was defined as lactic acid levels >5 mmol/l with bicarbonate <20 mmol/l. Possible risk factors, such as current and preceding NRTI-treatment as well as treatment with non-nucleoside reverse transcriptase inhibitors or protease inhibitors and concurrent liver disease, were analysed. RESULTS: Two hundred and twenty three asymptomatic HIV-infected patients were studied, including 174 patients (78%) on NRTI treatment, 12 patients (5%) treated without NRTIs and 37 patients (17%) not treated. Mild hyperlactataemia was found in 42 patients (19%), from whom 38/42 (90%) were NRTI-treated and the remaining patients (4/42, 10%) received no treatment (chi2, P<0.05). The significant risk factors for hyperlactataemia in the univariate analysis were NRTI-treatment as a group (P=0.03) and elevated ALT (P=0.008). In multivariate analysis NRTI use (P=0.05) and ALT level (P=0.03) remained a significant determinant of hyperlactataemia. Among the different individual NRTIs, a stavudine-containing (P=0.004) and a zalcitabine-containing (P=0.07) regimen were most notably associated with the development of hyperlactataemia, whereas for the combinations of NRTIs, such association was only found for stavudine/lamivudine (P=0.05). CONCLUSIONS: A correlation between hyperlactataemia and NRTI treatment was found, but the value of routine lactate measurement for individual treatment monitoring remains uncertain.

Trimethoprim-sulphamethoxazole as primary Pneumocystis carinii prophylaxis does not increase serum homocysteine levels in HIV-positive subjects.

Background: We recently observed that a short course of trimethoprim 300 mg b.i.d. in healthy volunteers can cause a substantial increase in fasting plasma homocysteine levels, up to concentrations reportedly associated with atherothrombotic complications. The purpose of this study was to determine whether primary Pneumocystis carinii prophylaxis (PCP) with trimethoprim-sulphamethoxazole (TMP-SMX) adversely affects serum homocysteine levels in HIV-positive patients. Methods: We studied 34 subjects [29 male, 5 female, mean age 36.8+/-7.9 (S.D.) years] with no prior AIDS-defining disease who required primary PCP prophylaxis (CD4+ T-cell count <200/mm(3)). The common dose of TMP-SMX was 80/400 mg (80 mg trimethoprim and 400 mg sulphamethoxazole) once daily. Serum total homocysteine levels were determined in four samples: two collected prior to the start of TMP-SMX and two collected on average 2.6+/-2.2 and 5.3+/-3.5 months into the first year of prophylactic therapy. Results: Mean serum homocysteine was 13.9+/-3.7 &mgr;mol/l pre-treatment and 14.4+/-5.0 &mgr;mol/l during treatment with TMP-SMX, a non-significant increase of 0.5 &mgr;mol/l (95% CI: -0.5 to +1.4, P=0.34). Folate levels were equally unaffected by TMP-SMX (13.1+/-6.5 nmol/l versus 13.3+/-5.3 nmol/l, before and during therapy, respectively). Baseline folate levels did not predict the response of homocysteine to TMP-SMX, and neither did age, gender, or serum creatinine. Conclusion: Long-term therapy with 80/400 mg TMP-SMX does not adversely affect homocysteine levels.

The effect of plasma drug concentrations on HIV-1 clearance rate during quadruple drug therapy.

OBJECTIVE: To investigate the relationship between exposure to antiretroviral drugs and the initial decline of plasma HIV-1 RNA. DESIGN: Open-label study in antiretroviral-naive HIV-1 infected patients using a quadruple drug regimen [nelfinavir (NFV), saquinavir (SQV), stavudine, and lamivudine]. METHODS: The elimination rate constant (k) for HIV-1 clearance was calculated during the first 2 weeks of treatment in 29 patients. Exposure to NFV and SQV was quantified on each study visit. Observed NFV and SQV concentrations were related to those expected in a reference population and a concentration ratio was calculated. The median concentration ratios for NFV and SQV, the baseline CD4+ lymphocyte count and baseline log10 HIV-1 RNA were correlated with k. RESULTS: A significant positive correlation was observed between k and the median NFV (P = 0.001) or SQV concentration ratio (P = 0.016) in univariate analysis. In multivariate analyses, the median NFV concentration ratio remained significantly correlated with k. CONCLUSIONS: The variation in the rate of decline of plasma HIV-1 RNA between patients after the initiation of a quadruple drug regimen could be explained by differences in exposure to NFV or SQV. Determination of k could be used to optimise further antiretroviral drug therapy and may be a first tool to assess antiretroviral activities of new or increasing doses of drugs administered in combination regimens. Furthermore, our data suggest that exposure to antiretroviral drugs should be incorporated in mathematical models to describe HIV-1 dynamics in more detail.

Maintenance therapy after quadruple induction therapy in HIV-1 infected individuals: Amsterdam Duration of Antiretroviral Medication (ADAM) study.

BACKGROUND: Highly active antiretroviral therapy (HAART) has led to health benefits for patients infected with HIV-1. However, long-term use of multidrug regimens is difficult to sustain. Simplifying antiretroviral treatment regimens would increase patients' adherence and minimise toxicity. We investigated the feasibility of a strategy of induction therapy followed by maintenance therapy with HAART in a randomised open-label study. METHODS: From March, 1997, we enrolled patients infected with HIV-1 with at least 200 CD4 cells/microL, at least 1000 HIV-1 RNA copies/mL in plasma, and no previous exposure to antiretroviral drugs. After 26 weeks of induction therapy (stavudine, lamivudine, saquinavir, and nelfinavir) patients were randomly allocated maintenance therapy (either stavudine and nelfinavir or saquinivir and nelfinavir) or prolonged induction therapy (if the plasma HIV-1 RNA concentration at weeks 24 and 25 was <50 copies/mL). FINDINGS: In February, 1998, we discontinued randomisation after an interim analysis. 62 patients had been enrolled. 39 (91%) of the 43 patients who were followed up for at least 26 weeks had an undetectable plasma HIV-1 RNA concentration at week 16. At week 26, 31 patients were randomly allocated treatment. Of these patients 25 had a total follow-up of at least 36 weeks. At week 36, a higher proportion of patients on maintenance therapy (nine [64%] of 14) had a detectable HIV-1 RNA than patients on prolonged induction therapy (one [9%] of 11, p=0.01). The initial virion-clearance rate during induction therapy was higher in five patients on maintenance therapy with a sustained undetectable plasma HIV-1 RNA concentration than in nine patients with recurrence of a detectable plasma HIV-1 RNA concentration at week 36 (0.35 vs 0.19 per day, respectively; p=0.0008). INTERPRETATION: The induction regimen provided a rapid suppression of viral replication to below 50 copies/mL. However, suppression was not sustained in a considerable number of patients who went onto maintenance therapy. It is currently inadvisable to continue attempts at moving from induction to maintenance therapy in day-to-day practice.