Treatment Interruption (treatment + interruption)

Distribution by Scientific Domains


Selected Abstracts


Non-medically supervised treatment interruptions among participants in a universally accessible antiretroviral therapy programme

HIV MEDICINE, Issue 5 2010
DM Moore
Background We examined clinical outcomes, patient characteristics and trends over time of non-medically supervised treatment interruptions (TIs) from a free-of-charge antiretroviral therapy (ART) programme in British Columbia (BC), Canada. Methods Data from ART-naļve individuals ,18 years old who initiated triple combination highly active antiretroviral therapy (HAART) between January 2000 and June 2006 were analysed. Participants having ,3 month gap in HAART coverage were defined as having a TI. Cox proportional hazards modelling was used to examine factors associated with TIs and to examine factors associated with resumption of treatment. Results A total of 1707 participants were study eligible and 643 (37.7%) experienced TIs. TIs within 1 year of ART initiation decreased from 29% of individuals in 2000 to 19% in 2006 (P<0.001). TIs were independently associated with a history of injection drug use (IDU) (P=0.02), higher baseline CD4 cell counts (P<0.001), hepatitis C co-infection (P<0.001) and the use of nelfinavir (NFV) (P=0.04) or zidovudine (ZDV)/lamivudine (3TC) (P=0.009) in the primary HAART regimen. Male gender (P<0.001), older age (P<0.001), AIDS at baseline (P=0.008) and having a physician who had prescribed HAART to fewer patients (P=0.03) were protective against TIs. Four hundred and eighty-eight (71.9%) participants eventually restarted ART with male patients and those who developed an AIDS-defining illness prior to their TI more likely to restart therapy. Higher CD4 cell counts at the time of TI and unknown hepatitis C status were associated with a reduced likelihood of restarting ART. Conclusion Treatment interruptions were associated with younger, less ill, female and IDU participants. Most participants with interruptions eventually restarted therapy. Interruptions occurred less frequently in recent years. [source]


Structured treatment interruption in patients with alveolar echinococcosis

HEPATOLOGY, Issue 2 2004
Stefan Reuter
In human alveolar echinococcosis (AE), benzimidazoles are given throughout life because they are only parasitostatic. It has been a longstanding goal to limit treatment, and recent reports suggest that, in selected cases, benzimidazoles may be parasitocidal. Previously, we showed that positron ,emission tomography (PET) using [18F]fluoro-deoxyglucose discriminates active from inactive lesions in AE. We have now performed a 3-year prospective study in 23 patients and conducted a structured treatment interruption in those without signs of PET activity. Disease progression was further assessed by ultrasound, computerized tomography, laboratory parameters, and clinical examination. We found PET-negative lesions in 15 of 23 patients and benzimidazoles were discontinued in these patients. After 18 months, patients were reevaluated, and, of the 15 initially PET-negative patients, 8 showed either new activity on PET (n = 6) or signs of clinical progression (n = 2). Reinitiation of benzimidazoles halted parasite growth again. No further progression was detected after 36 months. PET had a sensitivity of 91% for the detection of active lesions. In conclusion, despite successful suppression of metabolic activity, in most cases benzimidazoles do not kill the parasite. PET is a reliable tool for assessing metabolic activity and for timely detection of relapses. Neither duration of treatment, kind of treatment, lesion size, calcifications, or regressive changes reliably indicate parasite death. We discourage the discontinuation of benzimidazoles in inoperable AE even after many years of treatment. However, patients with a poor compliance of benzimidazole intake or patients suffering from side effects to benzimidazoles might be assessed for PET negativity. If permanent discontinuation of benzimidazoles is attempted, the course of disease should be followed by PET. (HEPATOLOGY 2004;39:509,517.) [source]


Long-term survival of HIV-infected patients treated with highly active antiretroviral therapy in Serbia and Montenegro

HIV MEDICINE, Issue 2 2007
DO Jevtovi
Background Highly active antiretroviral therapy (HAART) has dramatically changed the prognosis of HIV disease, even in terminally ill patients. Although these patients may survive many years after the diagnosis of AIDS if treated with HAART, some still die during treatment. Methods A retrospective study in a cohort of 481 HIV-infected patients treated with HAART between January 1998 and December 2005 was conducted to compare subgroups of long-term survivors (LTSs) and patients who died during treatment. Results A total of 48 patients survived for more than 72 months (mean 83.8±standard deviation 5.6 months). Thirty patients died during treatment (mean 35.3±25.0 months), of whom nine died from non-AIDS-related causes, 18 died from AIDS-related causes, and three died as a result of HAART toxicity. Although LTSs were significantly (P=0.015) younger at HAART initiation, age below 40 years was not a predictor of long-term survival. The subgroups did not differ in the proportion of clinical AIDS cases at HAART initiation, in the prevalence of hepatitic C virus (HCV) coinfection, or in pretreatment and end-of-follow-up CD4 cell counts. In contrast, the viral load achieved during treatment was lower in the survivors (P=0.03), as was the prevalence of hepatitis B virus (HBV) coinfection (P=0.03). Usage of either protease inhibitor (PI)-containing regimens [odds ratio (OR) 9.0, 95% confidence interval (CI) 2.2,35.98, P<0.001] or all three drug classes simultaneously (OR 7.4, 95% CI 2.2,25.1, P<0.001) was associated with long-term survival. Drug holidays incorporated in structured treatment interruption (STI) were also associated with a good prognosis (OR 14.9, 95% CI 2.9,75.6, P<0.001). Conclusions Long-term survival was associated with PI-based HAART regimens and lower viraemia, but not with the immunological status either at baseline or at the end of follow up. STI when CD4 counts reach 350 cells/,L, along with undetectable viraemia, was a strong predictor of long-term survival. [source]


Antiviral efficacy and resistance in patients on antiretroviral therapy in Kigali, Rwanda: the real-life situation in 2002

HIV MEDICINE, Issue 1 2006
A Fischer
Our study aimed to complete the published data on ARV therapy in Africa by describing the baseline situation in Rwanda before the launch of a large ARV programme (ESTHER). Prescription habits, frequency and reasons for treatment interruptions but also antiviral efficay, resistance to ARVs and genotypic variability of the viruses present in Rwanda were analysed. Among the 233 patients included in the study, it appeared that a vast majority (91%) were under triple therapy and that half of them had experienced at least one treatment interruption caused mainly by drug shortage or financial difficulties. Among 60 blood samples analysed, 26 were in virological failure with a viral load above 1000 RNA copies/ml and 11 presented major drug resistance mutations. Finally, virological failure could mainly be explained by the high frequency of treatment interruptions but also by the emergence of drug resistance mutations. Consequently the major objective for the ESTHER programme to improve the situation in Rwanda will be to reduce the drug shortage and facilitate the financial accessibility of the treatments. [source]


Extended antiretroviral treatment interruption in HIV-infected patients with long-term suppression of plasma HIV RNA

HIV MEDICINE, Issue 1 2005
CJ Achenbach
Objectives Evaluation of extended treatment interruption (TI) in chronic HIV infection among patients successfully treated with antiretroviral therapy. Methods An observational analysis of 25 patients in a prospectively followed cohort with chronic HIV infection, viral loads <500 HIV-1 RNA copies/mL for at least 6 months, and an interruption in therapy of ,28 days duration was carried out. Follow up was divided into 3-month time periods for analysis. The effects of time period, stratification group and stratification group by time period interactions on CD4 counts were tested using a mixed model. Univariate comparisons among patient characteristics and responses were performed using Fisher's exact test or the Wilcoxon rank sum test. Results At initiation of TI, the median CD4 count was 799 cells/,L. TI duration was a median of 7.1 months. HIV RNA rebounded to a median maximum level of 75 000 copies/mL. Maximum viral rebound was significantly greater in patients who were male, had lipodystrophy and had zenith HIV RNA prior to TI of ,50 000 copies/mL. Lower CD4 cell counts were observed during TI in patients with lipodystrophy, zenith HIV RNA ,50 000 copies/mL, history of AIDS, HIV infection ,5 years and presuppression CD4 count ,350 cells/,L. Patients who reinitiated therapy had shorter TI duration, presuppression CD4 count ,350 cells/,L, previous AIDS diagnosis and lipodystrophy. No patients developed adverse or AIDS-defining events during TI. Conclusions Long-term TI resulted in greater immune deterioration in patients with high viral set points or low CD4 cell counts prior to initiation of suppressive antiretroviral therapy. [source]


A high HIV DNA level in PBMCs at antiretroviral treatment interruption predicts a shorter time to treatment resumption, independently of the CD4 nadir

JOURNAL OF MEDICAL VIROLOGY, Issue 11 2010
Christophe Piketty
Abstract This study aimed to evaluate the safety of antiretroviral treatment interruption (TI) in HIV-infected patients who started treatment based on earlier guidelines, and to identify baseline factors predictive of the time to reach fixed criteria for treatment resumption. Prospective, open-label, multicenter trial. Patients were eligible if they had a CD4 cell count >350/mm3 and plasma HIV RNA <50,000,copies/ml when they first started antiretroviral therapy (ART); and if they had a CD4 count >450/mm3 and stable plasma HIV RNA <5,000,copies/ml for at least 6 months prior to enrolment. The criteria for ART resumption were a CD4 cell count <300/mm3 and/or a CDC stage B or C event. 116 patients had received ART for a median of 5.3 years. The median CD4 cell count and plasma HIV RNA values at inclusion were 809/mm3 and 2.6,log copies/ml, respectively. Median HIV DNA load at inclusion was 2.3,log copies/106 peripheral blood mononuclear cells (PBMCs). Thirty-six months after TI, 63.9% of the patients had not yet reached the criteria for ART resumption, and 55.9% of patients had not resumed ART. In Cox multivariable analysis, a high HIV DNA level at TI, a low CD4 nadir, and pre-existing AIDS status were the only significant risk factors for reaching the criteria for ART resumption (hazards ratio: 2.15 (1.02,4.53), 4.59 (1.22,17.24), and 5.74 (1.60,20.56), respectively). Patients who started ART with a CD4 cell count above 350/mm3 were able to interrupt treatment for long periods without a high absolute risk of either AIDS or severe non-AIDS morbidity/mortality. A high PBMC HIV DNA level at TI was a strong predictor for more rapid treatment resumption. J. Med. Virol. 82:1819,1828, 2010. © 2010 Wiley-Liss, Inc. [source]


Prognostic factors of long-term CD4+count-guided interruption of antiretroviral treatment

JOURNAL OF MEDICAL VIROLOGY, Issue 3 2009
L. Sarmati
Abstract Aim of the study was to determine predictors of the duration of antiretroviral treatment interruption in patients infected with HIV. This pilot prospective, open-label, multicenter trial comprised 62 HIV-seropositive subjects who decided voluntarily to interrupt therapy after two or more years of successful HAART. The primary end-point was the time to patients being free of therapy before reaching a CD4+ cell count ,350/µl. Fifteen of 62 patients remained in treatment interruption for more than 180 days. Patients restarting therapy had higher HIV-DNA levels (P,=,0.05), were treated more frequently with NNRTI-drugs (P,=,0.02), had a shorter period of HAART (P,=,0.046), and lower CD4+ cell counts after day 14 of interruption of treatment (P,=,0.04). Multivariate regression analysis showed that less than 323 baseline proviral HIV-DNA cp/106 PBMCs and more than 564 CD4 cells/µl at day 14 after interruption were associated independently with a reduced risk of restarting treatment (P,=,0.041 and P,=,0.012, respectively). A score based on CD4+ cell counts at nadir, at baseline, at week 2 of treatment interruption, and on baseline HIV-DNA values can identify patients with a prolonged period free safely of treatment. J. Med. Virol. 81:481,487, 2009. © 2009 Wiley-Liss, Inc. [source]


HIV-1 replication capacity and genotype changes in patients undergoing treatment interruption or lamivudine monotherapy,

JOURNAL OF MEDICAL VIROLOGY, Issue 2 2008
Nicola Gianotti
Abstract The objective of this study was to investigate the mechanisms underlying the virological and immunological changes occurring in failing HIV-1 infected patients undergoing treatment interruption or lamivudine monotherapy (the E-184V Study). Associations were sought between the de-selection of individual reverse transcriptase and protease resistance mutations and replication capacity recovery, HIV-RNA changes, and immunological changes. The replication capacity recovery was defined as the ratio between the replication capacity at weeks 24 or 48, and that measured at baseline. The replication capacity recovery, which was evaluable in 21 patients at week 24 and in 18 at week 48, was significantly higher in the treatment interruption than in the lamivudine group at week 24 (P,=,0.002). Forty-eight week replication capacity recovery was greater when the 184V (P,=,0.023), the 41L (P,=,0.02), or the 215Y mutation (P,=,0.037) were deselected at week 12. A greater reduction in the CD4+/CD8+ ratio at week 48 (P,=,0.038) was observed as the 184V mutation was deselected and the de-selection of the 184V mutation at week 12 was the only independent predictor of the change of the CD4+/CD8+ ratio at week 48 from baseline at multivariable analysis (F -value,=,6.72, P,=,0.021). In conclusion, among patients undergoing treatment interruption or lamivudine monotherapy, the recovery of HIV-1 replication capacity was associated with the de-selection of reverse transcriptase mutations. The de-selection of the 184V mutation predicts independently a reduction in the CD4+/CD8+ ratio. J. Med. Virol. 80:201,208, 2008. © 2007 Wiley-Liss, Inc. [source]


Favorable outcome of ex-vivo purging of monocytes after the reintroduction of treatment after interruption in patients infected with multidrug resistant HIV-1,

JOURNAL OF MEDICAL VIROLOGY, Issue 11 2007
Hamid Hasson
Abstract In multidrug resistant patients treatment interruptions allow the selection of archived wild-type drug-susceptible viruses that compete for the less fit drug-resistant strains. However, the selection of viruses with increased replicative capacity is often followed by a loss of CD4+ T cells. In addition, drug resistant variants later re-emerge limiting the overall clinical benefit of treatment interruption. Blood monocytes are a key component of the HIV reservoir and can be partially removed by a system for purging of myeloid cells (MYP). This study tested the safety and efficacy of MYP on multidrug resistant patients who underwent treatment interruption. Twelve patients were randomized to receive or not six cycles of MYP during treatment interruption. An optimized antiretroviral regimen was reintroduced after the reappearance of a drug susceptible genotype. Following therapy reintroduction, a long lasting increase in CD4+ T cell counts was observed only in the treatment interruption,+,MYP patients but not in the control patients. Five/six treatment interruption,+,MYP patients never experienced virological rebound during a median follow up period of 98 weeks. In contrast, 4/6 patients who did not receive MYP never reached complete viral suppression and had a virological rebound after a median of 16.5 weeks after treatment reintroduction. The difference between the two groups in the time to virological rebound was statistically significant (P,=,0.021). A consistent decrease of HIV DNA load in CD14+ purified cells was observed only in treatment interruption,+,MYP patients. These data suggest that MYP can improve the immunological and virological response to treatment interruption. J. Med. Virol. 79:1640,1649, 2007. © 2007 Wiley-Liss, Inc. [source]


Endocrine and Ovarian Responses to Prolonged Adrenal Stimulation at the Time of Induced Corpus Luteum Regression

REPRODUCTION IN DOMESTIC ANIMALS, Issue 6 2006
G Gabai
Contents The endocrine and ovarian responses to prolonged adrenal stimulation at the time of corpus luteum (CL) regression were studied in non-lactating non-pregnant Friesian cows. Cows were synchronized with two cloprostenol (PG) injections 11 days apart (second PG referred as time 0). Experiment 1 was carried out on five animals in two phases with a resting period in between. Between ,48 and 84 h, animals received 12 injections of either saline (CTR) or adrenocorticotrophic hormone (ACTH) agonist (Synacthen; SYN) every 12 h. Cortisol (C), progesterone (P4), oestradiol (E2) and LH were analysed in the blood samples collected every 8,12 h between days ,3 and 4. Pulsatile LH release was studied 4 h before and 4 h after naloxone administration beginning at 96 h. Experiment 2 was carried out on four cows in a cross-over experimental design (two phases, with a resting period in between). Treatments were performed by administering either saline (CTR) or Synacthen (SYN) every 12 h between ,36 and 24 h. The concentrations of C, P4 and E2 were measured in blood plasma every 4,12 h from days ,3 to 3, then every day from days 5 to 9. In both experiments, ovaries were examined by ultrasonography every 1,3 days. ACTH administration induced a significant increase (p < 0.001) of plasma C lasting for 7 days (experiment 1), and for 3,4 days (experiment 2). Plasma C returned to baseline levels within 6 days (expt 1) or 36 h (expt 2) after treatment interruption. During the SYN phase, LH pre-ovulatory surge was not detectable. During the CTR phase, naloxone administration induced a significant increase (p < 0.05) of average LH concentrations that was not evident during the SYN phase. The dominant follicle development was retarded and mean plasma E2 concentrations were significantly lower during the SYN phase (p < 0.01). Luteolysis was completed within 2 days. However, P4 decline between 0 and 4 h was slower (p < 0.01) during the SYN phase. Our results indicate that, under prolonged adrenal stimulation, follicular development is delayed and LH release is impaired, which are independent of CL function. [source]


Poor radiotherapy compliance predicts persistent regional disease in advanced head/neck cancer,

THE LARYNGOSCOPE, Issue 3 2009
Urjeet A. Patel MD
Abstract Objective: To determine if poor compliance to chemoradiation results in an increased rate of persistent neck disease. Study Design: Retrospective, cohort study in an urban, tertiary-care medical center. Methods: The study included patients with N+ stage III/IV squamous cell carcinoma of the upper aerodigestive tract treated with curative-intent chemoradiation, who underwent subsequent planned neck dissection. Main outcome measure was persistent regional disease evidenced by identifiable carcinoma in neck dissection specimens. Variables including age, gender, race, primary site, initial T, N staging, imaging results, and treatment compliance were assessed and correlated to positive neck dissection pathology. Results: Of 40 patients, 18 (45%) had persistent carcinoma in neck dissection specimens while 22 (55%) demonstrated complete response in the neck. There were 14 patients (35%) who were poorly compliant to radiotherapy (,14 days treatment interruption) and the remaining 26 patients (65%) were considered compliant (<14 missed days). Only 23% of compliant patients had positive pathology while 79% of noncompliant patients had positive pathology (hazard ratio: 9.9). Noncompliance was the only variable that had a statistically significant correlation to positive pathology results (P = .002). Multivariate logistic regression showed all other variables to be insignificant in predicting pathology. Conclusions: This study found that poorly compliant patients are at significantly higher risk of persistent neck disease. Poor compliance may help identify patients who will most benefit from neck dissection after chemoradiation. This variable was more predictive than pretreatment variables and posttreatment CT scan. Further studies investigating patterns of failure after chemoradiotherapy in the poorly compliant patient population are warranted. Laryngoscope, 2009 [source]


Natalizumab dosage suspension: Are we helping or hurting?

ANNALS OF NEUROLOGY, Issue 3 2010
Timothy W. West MD
The risk of developing progressive multifocal leukoencephalopathy increases with the duration of treatment with natalizumab. Planned dosage interruptions have been proposed as a means of decreasing cumulative risk. The clinical consequences of dosage interruption were evaluated in a single center cohort of natalizumab-treated patients. Medical records were reviewed for 84 patients identified with multiple sclerosis who received 12 or more infusions of natalizumab at an academic multiple sclerosis center. Eighty-one percent (68/84) underwent a dosage interruption, and 19% (16/84) had no interruption in natalizumab treatment. Of those with a treatment interruption, 27.9% (19/68) experienced a clinical relapse within 6 months of the suspension, whereas none of the patients with ongoing treatment experienced a flare during months 12 to 18 of treatment (p = 0.017, Fisher exact test). Survival analysis showed that Kaplan-Meier curves comparing dosage interruption to ongoing treatment diverged (p = 0.025). Median time from treatment interruption to relapse onset was 3 months. No clinical predictors associated with an increased risk of developing flares during dosage interruption were identified. Among the 19 patients who had a flare, 7 had severe flares, with a mean number of 16 Gad+ lesions on brain magnetic resonance imaging (range, 6,40). Their median Expanded Disability Status Scale at natalizumab interruption was 3.0 and increased to 6.0 during the flare (p = 0.0008). Natalizumab dosage interruption is associated with clinical flares and return of radiographic inflammatory disease activity. Some of these flares can be clinically severe, with a high number of contrast-enhanced lesions, suggesting a possible rebound of disease activity. Ann Neurol 2010;68:395,399 [source]


The successful management of two pregnancies with wild type metastatic gastrointestinal stromal tumors

ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 3 2009
Thean Hsiang TAN
Abstract Aim: To discuss the management of the uncommon situation of metastatic gastrointestinal tumour coexisting with pregnancy. Method: We describe two cases of women with metastatic gastrointestinal stromal tumor (GIST) who successfully achieved a full-term pregnancy without complications and with the delivery of healthy infants. In both cases, treatment with imatinib mesylate was withheld during pregnancy because of its unknown effects and questionable safety for the developing fetus. The available data in the medical literature regarding the use and safety of imatinib and pregnancy are reviewed. We also examine whether the knowledge of the exon mutational status would have influenced treatment decisions. Results: Both women had wild type GIST, but with different tumor growth characteristics, treatment responses and outcomes. The first patient deferred imatinib therapy to fall pregnant and her disease progressed rapidly off treatment. The second patient had a more indolent GIST where active surgical management allowed her to experience a long durable clinical response. She potentially belongs to a pediatric subgroup which carries a better prognosis despite being off imatinib. Conclusion: While we have successfully managed two pregnant women with metastatic GIST, the issue of initiating imatinib therapy in treatment-naive women, and treatment interruption in women already on therapy, remain difficult areas. Patients and their partners need to make an informed choice regarding the associated risks and the potential long-term sequelae if pregnancies are contemplated. Further research into the natural history of wild type GIST and how to tailor subsequent treatment are needed. [source]


Risk of diarrhoea in a long-term cohort of renal transplant patients given mycophenolate mofetil: the significant role of the UGT1A8*2 variant allele

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 6 2010
Jean-Baptiste Woillard
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , Mycophenolate mofetil (MMF), the most widely used drug in allograft transplantation, is subject to hepatic and intestinal glucuronidation and entero-hepatic cycling. , Diarrhoea is its most frequent adverse event leading to non-compliance, treatment interruption and ultimately to an increased rate of acute rejection. , Cyclosporin reduces the biliary excretion of mycophenolate metabolites, presumably by inhibiting the efflux transporter MRP2. , When combined with MMF, cyclosporin reduces the incidence of diarrhoea, suggesting the role played by biliary excretion of mycophenolate glucuronides in this adverse event. WHAT THIS STUDY ADDS , In a long-term cohort of renal transplant patients on MMF, the two factors significantly associated with a reduced incidence of diarrhoea were the co-medication with cyclosporin (as opposed to tacrolimus or sirolimus) and the *2 variant allele of the intestinal UGT1A8. , Polymorphisms in the other UDP-glucuronosyl-transferases and MRP2 were not significant. AIM In renal transplant patients given mycophenolate mofetil (MMF), we investigated the relationship between the digestive adverse events and polymorphisms in the UGT genes involved in mycophenolic acid (MPA) intestinal metabolism and biliary excretion of its phase II metabolites. METHODS Clinical data and DNA from 256 patients transplanted between 1996 and 2006 and given MMF with cyclosporin (CsA, n = 185), tacrolimus (TAC, n = 49) or sirolimus (SIR, n = 22), were retrospectively analysed. The relationships between diarrhoea and polymorphisms in UGT1A8 (*2; 518C>G, *3; 830G>A), UGT1A7 (622C>T), UGT1A9 (,275T>A), UGT2B7 (,840G>A) and ABCC2 (,24C>T, 3972C>T) or the co-administered immunosuppressant were investigated using the Cox proportional hazard model. RESULTS Multivariate analysis showed that patients on TAC or SIR had a 2.8 higher risk of diarrhoea than patients on CsA (HR = 2.809; 95%CI (1.730, 4.545); P < 0.0001) and that non-carriers of the UGT1A8*2 allele (CC518 genotype) had a higher risk of diarrhoea than carriers (C518G and 518GG genotypes) (HR = 1.876; 95%CI (1.109, 3.175); P = 0.0192). When patients were divided according to the immunosuppressive co-treatment, a significant effect of UGT1A8*2 was found in those co-treated with CsA (HR = 2.414; 95%CI (1.089, 5.354); P = 0.0301) but not TAC or SIR (P = 0.4331). CONCLUSION These results suggest that a possible inhibition of biliary excretion of MPA metabolites by CsA and a decreased intestinal production of these metabolites in UGT1A8*2 carriers may be protective factors against MMF-induced diarrhoea. [source]


Absence of favourable changes in circulating levels of interleukin-16 or ,-chemokine concentration following structured intermittent interruption treatment of chronic human immunodeficiency virus infection

CLINICAL MICROBIOLOGY AND INFECTION, Issue 1 2005
M. Montes de Oca Arjona
Abstract Changes in virological and immunological parameters were analysed following structured intermittent interruption of highly active anti-retroviral therapy (HAART) of patients with chronic human immunodeficiency virus (HIV) infection. Parameters analysed were serum levels of the CD8+ T-cell-derived inhibitory molecules interleukin-16 (IL-16), monocyte inhibitory protein-1, (MIP-1,) and RANTES (,regulated upon activation, normal T-cell expressed and presumably secreted'), and the enhancer of HIV replication, monocyte chemotactic protein-1 (MCP-1). Twenty-five patients with chronic HIV infection were evaluated during three cycles of intermittent interruptions of therapy (8 weeks on/4 weeks off) in comparison with 20 healthy sex- and age-matched controls. At enrolment, HIV-infected patients showed significantly higher serum concentrations of IL-16 and RANTES, and significantly lower concentrations of MCP-1, than did healthy controls. Levels of MIP-1, were similar in both groups. Only the serum levels of IL-16 increased significantly in HIV-infected patients after every treatment interruption. However, differences between the CD4+ or CD8+ T-cell counts/µL, HIV loads and serum concentrations of each cytokine at baseline and at the end of the three cycles of intermittent interruptions of therapy were not significant. It was concluded that structured intermittent interruption of HAART for patients with chronic HIV infection did not modify the immunological parameters, including serum levels of CD8+ T-cell-derived inhibitory molecules, or the virus parameters studied. Thus, the findings do not support the use of this treatment modality for the management of HIV-infected patients. [source]


Non-medically supervised treatment interruptions among participants in a universally accessible antiretroviral therapy programme

HIV MEDICINE, Issue 5 2010
DM Moore
Background We examined clinical outcomes, patient characteristics and trends over time of non-medically supervised treatment interruptions (TIs) from a free-of-charge antiretroviral therapy (ART) programme in British Columbia (BC), Canada. Methods Data from ART-naļve individuals ,18 years old who initiated triple combination highly active antiretroviral therapy (HAART) between January 2000 and June 2006 were analysed. Participants having ,3 month gap in HAART coverage were defined as having a TI. Cox proportional hazards modelling was used to examine factors associated with TIs and to examine factors associated with resumption of treatment. Results A total of 1707 participants were study eligible and 643 (37.7%) experienced TIs. TIs within 1 year of ART initiation decreased from 29% of individuals in 2000 to 19% in 2006 (P<0.001). TIs were independently associated with a history of injection drug use (IDU) (P=0.02), higher baseline CD4 cell counts (P<0.001), hepatitis C co-infection (P<0.001) and the use of nelfinavir (NFV) (P=0.04) or zidovudine (ZDV)/lamivudine (3TC) (P=0.009) in the primary HAART regimen. Male gender (P<0.001), older age (P<0.001), AIDS at baseline (P=0.008) and having a physician who had prescribed HAART to fewer patients (P=0.03) were protective against TIs. Four hundred and eighty-eight (71.9%) participants eventually restarted ART with male patients and those who developed an AIDS-defining illness prior to their TI more likely to restart therapy. Higher CD4 cell counts at the time of TI and unknown hepatitis C status were associated with a reduced likelihood of restarting ART. Conclusion Treatment interruptions were associated with younger, less ill, female and IDU participants. Most participants with interruptions eventually restarted therapy. Interruptions occurred less frequently in recent years. [source]


Antiviral efficacy and resistance in patients on antiretroviral therapy in Kigali, Rwanda: the real-life situation in 2002

HIV MEDICINE, Issue 1 2006
A Fischer
Our study aimed to complete the published data on ARV therapy in Africa by describing the baseline situation in Rwanda before the launch of a large ARV programme (ESTHER). Prescription habits, frequency and reasons for treatment interruptions but also antiviral efficay, resistance to ARVs and genotypic variability of the viruses present in Rwanda were analysed. Among the 233 patients included in the study, it appeared that a vast majority (91%) were under triple therapy and that half of them had experienced at least one treatment interruption caused mainly by drug shortage or financial difficulties. Among 60 blood samples analysed, 26 were in virological failure with a viral load above 1000 RNA copies/ml and 11 presented major drug resistance mutations. Finally, virological failure could mainly be explained by the high frequency of treatment interruptions but also by the emergence of drug resistance mutations. Consequently the major objective for the ESTHER programme to improve the situation in Rwanda will be to reduce the drug shortage and facilitate the financial accessibility of the treatments. [source]


Favorable outcome of ex-vivo purging of monocytes after the reintroduction of treatment after interruption in patients infected with multidrug resistant HIV-1,

JOURNAL OF MEDICAL VIROLOGY, Issue 11 2007
Hamid Hasson
Abstract In multidrug resistant patients treatment interruptions allow the selection of archived wild-type drug-susceptible viruses that compete for the less fit drug-resistant strains. However, the selection of viruses with increased replicative capacity is often followed by a loss of CD4+ T cells. In addition, drug resistant variants later re-emerge limiting the overall clinical benefit of treatment interruption. Blood monocytes are a key component of the HIV reservoir and can be partially removed by a system for purging of myeloid cells (MYP). This study tested the safety and efficacy of MYP on multidrug resistant patients who underwent treatment interruption. Twelve patients were randomized to receive or not six cycles of MYP during treatment interruption. An optimized antiretroviral regimen was reintroduced after the reappearance of a drug susceptible genotype. Following therapy reintroduction, a long lasting increase in CD4+ T cell counts was observed only in the treatment interruption,+,MYP patients but not in the control patients. Five/six treatment interruption,+,MYP patients never experienced virological rebound during a median follow up period of 98 weeks. In contrast, 4/6 patients who did not receive MYP never reached complete viral suppression and had a virological rebound after a median of 16.5 weeks after treatment reintroduction. The difference between the two groups in the time to virological rebound was statistically significant (P,=,0.021). A consistent decrease of HIV DNA load in CD14+ purified cells was observed only in treatment interruption,+,MYP patients. These data suggest that MYP can improve the immunological and virological response to treatment interruption. J. Med. Virol. 79:1640,1649, 2007. © 2007 Wiley-Liss, Inc. [source]


A randomised controlled trial of moxibustion for breech presentation

BJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 6 2005
Francesco Cardini
Objectives To evaluate the efficacy of moxibustion for the correction of fetal breech presentation in a non-Chinese population. Design Single-blind randomised controlled trial (RCT). Setting Six obstetric departments in Italy. Sample Healthy non-Chinese nulliparous pregnant women at 32,33 weeks + 3 days of gestational age with the fetus in breech presentation. Methods Random assignment to treatment or observation. Treatment consisted of moxibustion (stimulation with heat from a stick of Artemisia vulgaris) at the BL 67 acupuncture point (Zhiyin) for one or two weeks. Two weeks after recruitment, each participant was subjected to an ultrasonic examination of the fetal presentation. Main outcome measure Number of participants with cephalic presentation in the 35th week. Results The study was interrupted when 123 participants had been recruited (46% of the planned sample). Intermediate data monitoring revealed a high number of treatment interruptions. At this point no difference was found in cephalic presentation in the 35th week (treatment group: 22/65, 34%; control group: 21/58, 36%; RR 0.95; 99% CI 0.59,1.5). Conclusions The results underline the methodological problems evaluating of a traditional treatment transferred from a different cultural context. They do not support either the effectiveness or the ineffectiveness of moxibustion in correcting fetal breech presentation. [source]