Home About us Contact
|
Home About us Contact | ||
|
|
||
Antiretroviral Regimens (antiretroviral + regimen)
Selected AbstractsIncidence and risk factors of bacterial pneumonia requiring hospitalization in HIV-infected patients started on a protease inhibitor-containing regimenHIV MEDICINE, Issue 4 2006V Le Moing Objectives To describe the incidence and risk factors of bacterial pneumonia occurring in patients treated with antiretrovirals. Methods In the ongoing APROCO (Anti-proteases) cohort, 1281 patients at the initiation of a protease inhibitor (PI)-containing antiretroviral regimen were enrolled from 1997,1999. All events requiring hospitalization during follow up are recorded. Of these, bacterial pneumonia was defined as the occurrence of a new pulmonary infiltrate with fever and either evidence of a bacteriological cause (definite cases) or favourable outcome with antimicrobial therapy (presumptive cases). Risk factors of bacterial pneumonia were studied using survival analyses. Results During a median follow up of 43 months, 29 patients had at least one episode of bacterial pneumonia, giving an incidence of 0.8/100 patient years. The 11 definite cases were attributable to Streptococcus pneumoniae (n=9), Legionella pneumophila (n=1) and Haemophilus influenzae (n=1). In multivariate analysis, bacterial pneumonia was significantly more frequent in older patients, injecting drug users, patients having a CD4 cell count>500 cells/,L at baseline and patients who initiated PI therapy with nonboosted saquinavir. It was significantly less frequent in nonsmokers. The occurrence of bacterial pneumonia was also associated with lower self-reported adherence to antiretroviral therapy and to higher plasma HIV-1 RNA levels during follow-up. Conclusions Bacterial pneumonia occurs rarely in patients treated with a PI-containing regimen and may be associated with virological failure. [source] Determinants of adherence to highly active antiretroviral therapy (HAART) in Chinese HIV/AIDS patientsHIV MEDICINE, Issue 2 2003OW Fong Objective Drug adherence is crucial to the success of highly active antiretroviral therapy (HAART) in the treatment of HIV disease. Adherence to HAART and its determinants may, however, differ across HIV/AIDS populations. Methods We retrospectively studied drug adherence by self-report in HIV-1 infected Chinese patients who have been on HAART for at least 1 year as at the end of year 2000. HAART is defined as three or more antiretrovirals with at least one protease inhibitor or non-nucleoside analogue reverse transcriptase inhibitor. Results The last drug adherence level assessed by self-report in 161 Chinese patients were: grade A (100%) , 130, 80.7%; grade B (95,99%) , 25, 15.5%; grade C (90,94%) , three, 1.9% and grade D (< 90%) , three, 1.9%. Patients with full adherence were more likely to have undetectable (< 500 copies/mL) plasma virus level (adjusted OR, 4.22; 95% CI, 1.75,12.33). Patients' demographics, HIV disease status and antiretroviral regimen did not affect adherence. Partial drug adherence was, however, independently associated with the psychosocial factors of missing clinic appointments (adjusted OR, 3.13; 95% CI, 1.23,8.33), forgetfulness (adjusted OR, 4.55; 95% CI, 1.64,12.5) and a busy work life (adjusted OR, 6.67; 95% CI, 1.75,25). Conclusion There were similarities and differences in determinants affecting HAART adherence in Chinese compared with other patients. Psychosocial factors rather than HIV disease or treatment were more important factors in our Chinese patients. The relevance of patient populations and care setting for adherence to HAART shall be further studied. [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 2007Hamid 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] Clinical and Magnetic Resonance Imaging Regression of Progressive Multifocal Leukoencephalopathy in an AIDS Patient After Intensive Antiretroviral TherapyJOURNAL OF NEUROIMAGING, Issue 3 2001Rita A. Shapiro DO ABSTRACT A 36-year-old homosexual man with 6 months of visual symptoms and headaches had right homonymous hemianopia, mild new learning impairment, and alexia with agraphia. The initial brain magnetic resonance imaging (MRI) scan was reported consistent with left occipital infarction. Subsequent MRI demonstrated abnormal demyelination in the subcortical white matter and deep parieto-occipital white matter bilaterally, but primarily left. Human immunodeficiency virus testing and cerebrospinal fluid polymerase chain reaction for JC virus DNA were both positive, consistent with progressive multifocal leukoencephalopathy (PML) with AIDS. His clinical status steadily deteriorated, and MRI white matter abnormalities worsened despite high-dose antiretroviral therapy. After the antiretroviral regimen was intensified by the addition of a protease inhibitor, rapid clinical and radiographic improvement occurred with subsequent MRI studies revealing only residual left parieto-occipital encephalomalacia. PML in AIDS patients has been associated with a nearly uniformly poor prognosis until recent reports of improved outcomes after highly active antiretroviral therapy. This patient with PML and AIDS similarly showed a robust clinical and MRI response to intensive antiretroviral combination therapy, which has been maintained for more than 3 years. [source] Intracellular and plasma steady-state pharmacokinetics of raltegravir, darunavir, etravirine and ritonavir in heavily pre-treated HIV-infected patientsBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 5 2010Rob Ter Heine WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , The combination of raltegravir, etravirine and ritonavir boosted darunavir is a potent antiretroviral regimen for patients who have been heavily pre-treated for HIV-infection. All these agents have to exert their action intracellularly. However, only little is known about the cellular pharmacology of these agents. WHAT THIS STUDY ADDS , We investigated the steady-state plasma and cellular pharmacokinetics of raltegravir, etravirine, darunavir and ritonavir and the observed distinct intracellular accumulation ratios indicated that these antiretroviral drugs have different affinity for the cellular compartment. AIM To study the steady-state plasma and intracellular pharmacokinetics of raltegravir, etravirine, darunavir and ritonavir in heavily pre-treated patients. METHODS Patients on a salvage regimen containing raltegravir, etravirine, darunavir and ritonavir were eligible for inclusion. During a 12 h dosing interval plasma and peripheral blood mononuclear cells were collected. Drug concentrations were measured using a validated LC-MS/MS assay and pharmacokinetic analysis was performed using non-linear mixed effect modelling. RESULTS Irregular absorption was observed with raltegravir and darunavir, which may be caused by enterohepatic cycling. Relative bioavailability of ritonavir was low, when compared with other ritonavir regimens. Raltegravir plasma pharmacokinetics showed wide interpatient variability, while intracellular raltegravir concentrations could not be detected (<0.001 mg l,1 in cell lysate). The intracellular to plasma ratios for etravirine, darunavir and ritonavir were 12.9, 1.32 and 7.72, respectively, and the relative standard error of these estimates were 16.3%, 12.3% and 13.0%. CONCLUSIONS The observed distinct intracellular accumulation indicated that these drugs have different affinity for the cellular compartment. The relatively high intracellular accumulation of etravirine may explain its efficacy and its previously described absence of PK,PD relationships in the therapeutic concentration range, when compared with other non-nucleoside reverse transcriptase inhibitors. Lastly, the intracellular concentrations of ritonavir seem sufficient for inhibition of viral replication in the cellular compartment in PI-naive patients, but not in patients with HIV harbouring PI resistance. [source] Treatment outcomes amongst previously antiretroviral-naïve HIV-infected patients starting lopinavir/ritonavir-containing antiretroviral regimens at the Royal Free Hospital,HIV MEDICINE, Issue 1 2007CJ Smith Objective To describe outcomes in patients starting first-line antiretroviral regimens including lopinavir/ritonavir (LPV/r) in a routine clinic setting. Methods Previously naïve patients starting LPV/r-containing antiretroviral therapy were included in the study. Virological failure was defined as the first of two viral loads >500 HIV-1 RNA copies/mL more than 6 months after starting LPV/r. Cumulative percentages experiencing virological failure were calculated using Kaplan,Meier methods. Results A total of 195 individuals had a median follow-up time of 1.7 years. At 48 weeks, 87.9, 77.4 and 71.6% of patients with pretreatment CD4 counts of <50, 50,200 and >200 cells/,L, respectively, remained on LPV/r. By 48, 72 and 96 weeks, 2.2, 3.0 and 5.0% of patients, respectively, had experienced virological failure, ignoring treatment changes but censoring follow-up at discontinuation of all antiretrovirals; these percentages became 24.0, 33.7 and 42.3% when LPV/r discontinuation was considered as virological failure. Censoring those who stopped LPV/r with a viral load <50 copies/mL and considering as virological failures those who stopped LPV/r with a viral load >50 copies/mL gave 12.1, 14.6 and 17.0% virological failure at 48, 72 and 96 weeks, respectively. Median CD4 count increases at 24, 48 and 72 weeks were 167, 230 and 253 cells/,L, respectively. Conclusions Few patients experienced virological failure whilst on a LPV/r-based regimen, although it was not uncommon for patients in our clinic with higher baseline CD4 counts to discontinue LPV/r. [source] Long-term assessment of nevirapine-containing highly active antiretroviral therapy in antiretroviral-naive HIV-infected patients: 3-year follow-up of the VIRGO studyHIV MEDICINE, Issue 7 2006V Reliquet Objectives Data on the durability of antiretroviral regimens over a 3-year period have only rarely been reported. The aim of this study was to evaluate the long-term efficacy and safety of one or two daily doses of nevirapine (NVP), in combination with stavudine (d4T) and didanosine (ddI), in HIV-infected patients. Methods This study was a follow-up of the VIR (amune) Grand Ouest (VIRGO) study, a 12-month open-label trial to assess the safety and immunovirological activity of NVP-d4T-ddI combination therapy in antiretroviral-naive HIV-1-infected adults with baseline CD4 counts ,200 cells/,L and plasma viral loads ,5000 HIV-1 RNA copies/mL. Of the 100 patients included in the study, the 67 patients remaining on the initial triple therapy at the end of the study (1 year) were offered an extra 24 months of follow-up. Results Of the 60 patients who extended follow-up, 46 were still being treated with d4T-ddI-NVP at month 36; 91% (39/43) had a plasma viral load <500 copies/mL (data were missing for three patients). CD4 cell counts increased over 36 months. Safety and tolerance were good with no unexpected long-term toxicity. Conclusion After 3 years of treatment with NVP-d4T-ddI, nearly half of the patients were still receiving the initial antiretroviral therapy with a sustained and durable immunovirological benefit. Long-term toxicity was mainly related to the nucleoside reverse transcriptase inhibitor components of the regimen. [source] Clinical implications of stopping nevirapine-based antiretroviral therapy: relative pharmacokinetics and avoidance of drug resistanceHIV MEDICINE, Issue 3 2004NE Mackie Objective To determine the pharmacokinetics of cessation of nevirapine (NVP) in order to design clinical protocols which will reduce the risk of resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs). Methods In a case study, NNRTI genotypic resistance was demonstrated in a patient discontinuing therapy for toxicity. Subsequently, nine patients receiving NVP-containing antiretroviral regimens and stopping treatment were recruited. Patients were advised to continue the nucleoside analogue reverse transcriptase inhibitor (NRTI) backbone for 5 days following cessation of NVP. Plasma NVP concentrations were determined over 7,10 days after the last dose. HIV-1 reverse transcriptase genotyping was performed at viral load rebound (approximately day 21 following cessation) to detect mutations associated with reduced NNRTI sensitivity. Results The median predicted time for plasma NVP concentration to fall below the inhibitory concentration (IC)50 of wild-type virus was 168 h (range 108,264 h). De novo genotypic mutations conferring resistance to NRTIs or NNRTIs were not demonstrated following cessation of therapy. Conclusions The prolonged elimination half-life of NVP compared with NRTIs, which persists even after 20 weeks of therapy, raises concern over the development of NNRTI resistance if all three drugs are stopped together. Continuation of the NRTI backbone for a further 5 days, allowing the elimination of NVP, may avoid the development of drug resistance. [source] Systematic review of the efficacy of antiretroviral therapies for reducing the risk of mother-to-child transmission of HIV infectionJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 3 2007N. Suksomboon PhD Summary Objective:, To evaluate the efficacy of antiretroviral therapies in reducing the risk of mother-to-child transmission of HIV infection. Methods:, Systematic review and meta-analysis of randomized controlled trials. Clinical trials of antiretrovirals were identified through electronic searches (MEDLINE, EMBASE, BIOSIS, EBM review and the Cochrane Library) up until November 2006. Historical searches of reference lists of relevant randomized controlled trials, and systematic and narrative reviews were also undertaken. Studies were included if they were (i) randomized controlled trials of any antiretroviral therapy aimed at decreasing the risk of mother-to-child transmission of HIV infection, (ii) reporting outcomes in terms of HIV infection in infant, infant death, stillbirth, premature delivery, or low birth weight. The data were extracted by a single investigator and checked by a second investigator. Disagreements were resolved through discussion or a third investigator. The efficacy was estimated using relative risk (RR), risk difference (RD) and number needed to treat (NNT) together with 95% confidence intervals. Results:, Fifteen trials were included in the systematic review. Based on five placebo-controlled trials, a zidovudine regimen reduced the risk of mother-to-child transmission by 43% (95% CI: 29,55%). The incidence of low birth weight seems to be decreased with zidovudine (pooled RR 0·75, 95% CI: 0·57,0·99). The efficacy of short-short course of zidovudine was comparable with that of the long-short course. Nevirapine monotherapy given to mothers and babies as a single dose reduced the risk of vertical transmission compared with an intrapartum and post-partum regimen of zidovudine (RR 0·60, 95% CI: 0·41,0·87). Zidovudine plus lamivudine was effective in reducing the risk of maternal-child transmission of HIV (RR 0·63, 95% CI: 0·45,0·90). Adding zidovudine to single-dose nevirapine in babies was no more effective than nevirapine alone (pooled RR 0·88, 95% CI: 0·47,1·63), nor was there any significant difference between zidovudine plus lamivudine and nevirapine. In mothers who were treated with standard antiretroviral therapy, no additional benefit was observed with the addition of a single dose of nevirapine in mothers and newborns. In addition, for mothers who received zidovudine prophylaxis, a two-dose intrapartum/newborn nevirapine reduced the risk of HIV infection and death of babies by 68% (95% CI: 39,83%) and 80% (95% CI: 10,95%), respectively, when compared with placebo. Conclusions:, The available evidence suggests that zidovudine alone or in combination with lamivudine and nevirapine monotherapy is effective for the prevention of mother-to-child transmission of HIV. They may also be beneficial in reducing the risk of infant death. Different antiretroviral regimens appear to be comparably effective in reducing HIV transmission from mothers to babies. In mothers already receiving zidovudine prophylaxis, adding a single dose of nevirapine to mothers during labour and giving the same drug to infants may further decrease the risk of vertical transmission and infant death. [source] Ultrasensitive assessment of residual HIV viraemia in HAART-treated patients with persistently undetectable plasma HIV-RNA: A cross-sectional evaluationJOURNAL OF MEDICAL VIROLOGY, Issue 3 2009Stefano Bonora Abstract Improvements in HIV-RNA assays have made accurate detection of as few as 2 copies/ml possible. This study objective was the evaluation of ultrasensitive HIV-RNA quantitation (beneath current threshold: 50 copies/ml) in patients receiving different antiretroviral regimens. A cross-sectional, ultrasensitive measurement of HIV-RNA levels (detection limit: 2.5 HIV-RNA copies/ml) was performed in 154 HIV-1-infected patients receiving ARV therapy, all classed as full responders according to the 50 copies/ml cut-off. Patients were undergoing treatment with two nucleoside/nucleotide reverse transcriptase inhibitors (N/NtRTIs) plus nevirapine (NVP, n,=,48), efavirenz (EFV, n,=,57) or lopinavir/ritonavir (LPV/r, n,=,49). Undetectable HIV-RNA (<2.5 copies/ml) occurred in 29/48 (60.4%), 24/57 (42.1%) and 14/49 (28.6%) NVP, EFV and LPV/r recipients, respectively. Mean virological-suppression (<50 copies/ml) duration was 28.6 months (median,=,22, SD,=,17.8), and only in LPV/r recipients length of suppression was associated with significantly lower HIV-RNA levels (P,=,0.015). Mean nadir CD4+ cell count of 270 cells/mm3 (median,=,240, SD,=,194.5) was significantly lower in the LPV/r arm (P,<,0.001). Nadir CD4+ level correlated with virological suppression but had opposite trends between NVP (positive) and LPV/r (negative; two tailed P,=,0.01). Logistic regression analysis showed NVP was the only independent factor associated with virologic suppression. NVP has demonstrated a distinct virological advantage at sub-clinical viral loads, possibly due to its greater penetration in extra-vascular compartments, warranting further investigation in the context of persistent low-level viraemia in long-term HAART. J. Med. Virol. 81:400,405, 2009. © 2009 Wiley-Liss, Inc. [source] Antiretroviral genotypic resistance in plasma RNA and whole blood DNA in HIV-1 infected patients failing HAART,JOURNAL OF MEDICAL VIROLOGY, Issue 10 2008Annalisa Saracino Abstract The extent to which HIV-1 proviral DNA mutations cause clinically relevant antiretroviral resistance is still controversial. Paired plasma HIV-1 RNA and whole blood DNA were compared in patients failing HAART to investigate if the additional knowledge of archived mutations could improve the selection of potentially active drugs. Seventy-three HIV-1-infected patients with first/second HAART failure were studied before starting a new regimen based on RNA genotyping. Follow-up data after a 12-week therapy were available. DNA genotyping was retrospectively performed on stored whole blood samples and mutational profiles were compared to those from RNA. The mean number of IAS pol mutations was significantly higher in RNA (4.45,±,2.76) than in DNA (2.88,±,2.47) (P,<,0.001). DNA genotyping provided a 6% increase in detection of resistance-associated mutations. Among 64/73 patients showing discordant DNA/RNA profiles, 54 (84%) also differed for predicted active drugs. 16/73 (22%) patients had ,1 mutation revealed by DNA genotyping alone, probably affecting therapy success in 2/16. However, neither RNA/DNA discordance nor detection of isolated DNA mutations were statistically associated with outcome. In conclusion, plasma RNA remains the elective choice for HIV genotyping in patients with therapy failure, even if the detection of proviral resistance-associated mutations, not simultaneously found in RNA, is a frequent event. Therefore, in some cases DNA plus RNA genotyping might assist in choosing more accurately subsequent antiretroviral regimens. J. Med. Virol. 80:1695,1706, 2008. © 2008 Wiley-Liss, Inc. [source] Prevalence of the mutational pattern E44D/A and/or V118I in the reverse transcriptase (RT) gene of HIV-1 in relation to treatment with nucleoside analogue RT inhibitorsJOURNAL OF MEDICAL VIROLOGY, Issue 3 2002Brigitte Montes Abstract It has been reported that a new pattern of mutations, E44D/A and/or V118I, in the reverse transcriptase (RT) gene of HIV-1 confers a moderate level of resistance to lamivudine in the absence of the M184V mutation. The prevalence of this mutational pattern was studied in HIV-1 isolates obtained from 280 patients. These mutations were not identified in the RT sequences from 23 antiretroviral-naive patients but were detected in 82 (31.9%) of the 257 RT sequences obtained from nucleoside reverse transcriptase inhibitors (NRTI)-experienced patients. Mutation at codon 44 was identified in 41 patients (7 mutations E44A and 34 mutations E44D), mutation V118I was identified in 73 patients and a combination of mutations at codons 44 and 118 was found in 32 patients. Multivariate analysis showed an association between the E44D/A and/or V118I mutational pattern and the RT mutations D67N, T69D, L210W, and T215Y/F. No relationship was observed between this mutational pattern and the lamivudine-specific resistance mutation M184V. The prevalence of these mutations increased significantly with the number of drug regimens experienced and a prevalence of 42.4% was observed in patients who had received ,,4 antiretroviral regimens. A relationship was found between the E44D/A and/or V118I mutational pattern and experience with didanosine or stavudine but not with lamivudine. The results suggest that the development of the E44D/A and/or V118I mutational pattern is frequent in patients treated with NRTIs. Thymidine analogues and didanosine, but not lamivudine, could promote the development of these mutations. J. Med. Virol. 66:299-303, 2002. © 2002 Wiley-Liss, Inc. [source] Human immunodeficiency virus-associated neurocognitive disorders: Mind the gapANNALS OF NEUROLOGY, Issue 6 2010Justin C. McArthur MBBS Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HANDs) remain among the most common disorders in people infected with HIV, even in an era when potent antiretroviral therapy is widely deployed. This review discusses the clinical features of HANDs and the implications for more effective treatment. With the improved survival of individuals treated with antiretrovirals, comorbid conditions are increasingly salient, including particularly coinfection with hepatitis C and the effects of aging. This review attempts to answer why there appears to be a therapeutic gap between the salutary effects of antiretroviral regimens and normalization of neurological function. A second gap is found in the understanding of the pathophysiology of HANDs. This review addresses this and discusses the animal models that have helped to elucidate these mechanisms. Although triggered by productive HIV infection of brain macrophages, aberrant and sustained immune activation appears to play a major role in inducing HANDs, and may explain the often incomplete neurological response to highly active antiretroviral therapy. Novel therapies aimed at persistent central nervous system inflammation will be needed to close this gap. ANN NEUROL 2010;67:699,714 [source] | |||||||||||||||||||