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Biomedical subjects

Marchina E van der Ende

Publications and source records attributed to Marchina E van der Ende.

11 recordsLinked to original sources
PubMed2006

In vitro replication capacity of HIV-2 variants from long-term aviremic individuals.

To establish whether efficient suppression of virus replication in HIV-2-infected individuals is associated with low replicative capacity of HIV-2, replication kinetics of HIV-2 variants from long-term aviremic individuals was analyzed and compared with that of the relatively slow-replicating HIV-1 variants from asymptomatics and long-term nonprogressors (AS/LTNP). On average, HIV-2 from aviremic individuals had lower replication rates than HIV-1 variants from AS/LTNP in cells of 8 donors (0.45 log10 [range 0.14-0.77] vs. 0.58 log10 [range 0.32-0.99] pg RT/ml/day, P = 0.036). The relatively low replication rate of HIV-2 compared to HIV-1 variants was not related to different sensitivities to inhibition by CD8+ T cells or different degrees of infectivity. HIV-2 replication rates increased with progressive infection and with switch from CCR5 to CXCR4 usage. The relatively low replicative capacity of HIV-2 variants from aviremic individuals likely contributes to the low viral load and benign course of infection in these individuals.

Case-Control Studies↗
PubMed2005

Pharmacokinetics of once-daily lopinavir/ritonavir and the influence of dose modifications.

We studied the pharmacokinetics of lopinavir/ritonavir dosed at 800/200 mg a day in 20 HIV-1-infected patients, and evaluated the effect of dose modifications in the case of trough concentration (Ctrough) levels less than 1.0 mg/l. Ctrough levels after the daily administration of lopinavir/ritonavir were lower than with twice daily administration. Dose modifications in four patients with Ctrough levels less than 1.0 mg/l succeeded in only one patient. Therapeutic drug monitoring can identify patients with lower-than-expected lopinavir exposure in a larger study.

Dose-Response Relationship, Drug↗
PubMed2005

Nelfinavir and nevirapine side effects during pregnancy.

BACKGROUND: The risk of vertical transmission of HIV has been substantially reduced since the introduction of highly active antiretroviral therapy (HAART); however, the impact of taking HAART during pregnancy on the woman, the fetus and the infant is not yet understood. OBJECTIVE: To assess and compare tolerability, safety and efficacy of nelfinavir- or nevirapine-containing HAART in a cohort of pregnant and non-pregnant HIV-infected women in The Netherlands. DESIGN: Retrospective comparative study. METHODS: In 15 centres specializing in HIV in The Netherlands, data on patient characteristics, HAART, adverse events, viral load response, mode of delivery and HIV status of the neonate were obtained from medical records of HIV-infected pregnant women who received HAART during pregnancy between January 1997 and June 2003. These data were compared with a control group of HIV-infected non-pregnant women that was obtained from the Dutch HIV-monitoring foundation database. RESULTS: Data from 186 pregnant and 186 non-pregnant HIV-infected women using a nelfinavir- or nevirapine-containing regimen were analysed. The pregnant women were younger, used a nelfinavir containing regimen more often, had higher CD4 cell counts and lower HIV RNA levels. Nelfinavir-related gastrointestinal symptoms (P < 0.001), hyperglycaemia (P < 0.001) and nevirapine-related hepatotoxicity (P = 0.003) occurred more often during pregnancy. The risk of nevirapine-induced rash was not increased. No major adverse events occurred. CONCLUSION: Nelfinavir- or nevirapine-containing HAART regimens during pregnancy are well tolerated. Side effects of antiretroviral therapy are more frequent in pregnant than in non-pregnant women.

Adult↗
PubMed2005

Safety of long-term interruption of successful antiretroviral therapy: the ATHENA cohort study.

We studied the dynamics of CD4 cell counts after the interruption of virologically successful highly active antiretroviral therapy (HAART) in 139 patients. Changes in CD4 cell counts during HAART interruption followed a biphasic pattern: an initial rapid decline during the first month followed by a slow decrease. During 48 weeks of follow-up mean CD4 cell counts remained just above the mean pre-HAART level. This limits the feasibility of structured treatment interruptions for patients with low nadir CD4 cell counts.

Adult↗
PubMed2003

Clinical, immunological and virological response to different antiretroviral regimens in a cohort of HIV-2-infected patients.

OBJECTIVE: To assess the clinical, immunological and virological response and the emergence of resistance towards antiretroviral therapy (ART) in a cohort of HIV-2-infected patients. DESIGN: Observational study. PATIENTS: HIV-2-infected patients residing in the Netherlands. RESULTS: From 1995 to 2001 seven patients failed various ART regimens. The resistance mutations were analysed retrospectively. Development of mutations proved to be similar to that observed in HIV-1-infected patients, with the exception of a higher occurrence of the Q151M mutation within the reverse transcriptase gene. In a prospective study, comprising 13 consecutive naive HIV-2-infected patients, all patients achieved plasma HIV-2-RNA suppression below the detection limit (500 copies/ml). The antiretroviral regimen consisted of two nucleoside reverse transcriptase inhibitors (NRTIs) and indinavir, with a boosting dose of ritonavir; the median follow-up was 91 weeks. Two patients experienced a temporary virological rebound, while at the same time therapeutic drug monitoring showed sub-therapeutic plasma levels of indinavir. CONCLUSION: Sustained viral suppression in HIV-2-infected patients can be achieved using an antiretroviral regimen of two NRTIs and boosted indinavir or lopinavir.

Adult↗
PubMed2003

Treatment failure of nelfinavir-containing triple therapy can largely be explained by low nelfinavir plasma concentrations.

The relationship between plasma concentrations of nelfinavir and virologic treatment failure was investigated to determine the minimum effective concentration of nelfinavir. Plasma samples were prospectively collected from treatment-naive patients who began taking nelfinavir, 1,250 mg BID + two nucleoside reverse transcription inhibitors (NRTIs). Nelfinavir concentration ratios were calculated by dividing each individual nelfinavir level by the time-adjusted population value. Virologic failure was defined as either no response (a detectable viral load after 6 months) or a relapse (detectable viral load after being undetectable, or an increase in viral load >1 log above nadir). Forty-eight patients were included with a median follow-up period of 8 months. The median concentration ratio of nelfinavir was 0.98 (interquartile range, 0.76-1.47). Virologic failure was observed in 29% of the patients. In a univariate analysis, the nelfinavir concentration ratio appeared to be the single determinant that was related to virologic failure (P = 0.039). Patients with a median ratio <0.90 had a relative risk of 3.0 (95% CI, 1.2-7.6) for virologic failure. Using this threshold, virologic failures were detected with 64% sensitivity and 74% specificity (P = 0.014). Virologic failure of nelfinavir-containing triple therapy can be explained, to a large extent, by low plasma levels of nelfinavir.

Adult↗
PubMed2003

Low nevirapine plasma concentrations predict virological failure in an unselected HIV-1-infected population.

OBJECTIVE: To assess the relationship between plasma nevirapine concentrations and plasma HIV-1 RNA response in HIV-1-infected patients. DESIGN: An observational cohort analysis. METHODS: Plasma samples were obtained on a routine basis from 189 patients receiving nevirapine 200mg twice daily, and plasma nevirapine concentrations were measured with reversed phase high performance liquid chromatography. Patients were divided into two groups based on plasma nevirapine concentrations below (and equal to) or above 3 mg/L. The association between steady-state nevirapine concentrations and plasma HIV-1 RNA was determined by multivariate analysis. RESULTS: Out of 189 patients, 13 (7%) had low nevirapine plasma concentrations and 176 patients had concentrations above 3 mg/L. In total, 22 (12%) patients showed virological failure and 8 patients (4%) discontinued nevirapine because of adverse effects. The risk of failure in patients with nevirapine plasma concentrations </=3mg/L was increased (relative risk 5.0, 95% CI 1.8-13.7). Rashes and liver enzyme elevations each occurred in 8% of patients. CONCLUSIONS: Low nevirapine drug concentrations are predictive of virological failure.

Adult↗
PubMed2002

Post-exposure prophylaxis.

The mean risk of acquiring HIV after an occupational exposure, injecting drug use or sexual exposure varies from < 0.1 to 3%. A high plasma HIV-RNA of the source increases the risk of each of the exposures. Other factors, such as the volume of the inoculum involved to which the individual was exposed, other sexually transmitted diseases and ruptures of mucous membranes are associated with a higher risk of HIV transmission. Based on the calculated risk, post-exposure prophylaxis (PEP) should be recommended. In the Netherlands, prescription of PEP in the occupational setting is a standard procedure and has proved to be feasible. This was associated with a high percentage (62%) of mild and reversible toxicity and a small percentage (2%) of serious adverse events related to antiretroviral drugs, i.e. nephrolithiasis (due to indinavir) and toxic hepatitis (due to nevirapine). In The Netherlands so far no HIV-seroconversions have been recorded after an occupational accident.

Adult↗