The primary end point--viral load decay rate per day--was 0.13 log10 RNA copies/ml per day. Over 7 days, we observed a median 0.89 log10 decrease in HIV-1 viral load; seven individuals (44%) had a decrease of > 1 log10. The most significant adverse effects were grade I diarrhoea (31%) and a mild headache (25%). Steady-state drug levels were achieved by day 6.
STARTMRK, a phase III noninferiority trial of raltegravir-based versus efavirenz-based therapy in treatment-naive patients, remained blinded until its conclusion at 5 years. We now report the final study results.
In 2001 an antiretroviral treatment programme was initiated with the first-line regimen stavudine, lamivudine and efavirenz. In 2003, the fixed-dose combination of stavudine, lamivudine and nevirapine was recommended. Thus, first-line therapy was changed and FDN was initiated when patients were switched from efavirenz to nevirapine.
sustiva dosage form
The use of fixed-dose combination nucleoside reverse-transcriptase inhibitors (NRTIs) with a nonnucleoside reverse-transcriptase inhibitor or a ritonavir-boosted protease inhibitor is recommended as initial therapy in patients with human immunodeficiency virus type 1 (HIV-1) infection, but which NRTI combination has greater efficacy and safety is not known.
sustiva missed dose
Mexico started scaling-up access to antiretroviral treatment in the late 1990s. Even though the Mexican Health System enrolled patients at impressive speed, in the initial years important aspects of the quality of care were overlooked.
Rate constants of artemisinin, bupropion, propofol and efavirenz metabolism by human liver microsomes from a panel of 12 donors, with different levels of CYP2B6 activity, were estimated in WinNonlin. Correlations between the metabolic rate constant for artemisinin and the other CYP2B6 substrates were examined.
sustiva drug classification
Samples of efavirenz (EFZ) were evaluated to investigate the influence of the micronization process on EFZ stability. A combination of X-ray diffraction, thermal analysis, FTIR, observations of isotropic chemical shifts of (1)H in distinct solvents, their temperature dependence and spin-lattice relaxation time constants (T1), solution (1D and 2D) (13)C nuclear magnetic resonance (NMR), and solid-state (13)C NMR (CPMAS NMR) provides valuable structural information and structural elucidation of micronized EFZ and heptane-recrystallized polymorphs (EFZ/HEPT). This study revealed that the micronization process did not affect the EFZ crystalline structure. It was observed that the structure of EFZ/HEPT is in the same form as that obtained from ethyl acetate/hexane, as shown in the literature. A comparison of the solid-state NMR spectra revealed discrepancies regarding the assignments of some carbons published in the literature that have been resolved.
HIV-1 viral load (VL) monitoring is recommended but seldom performed in resource-constrained countries. An evaluation of patients receiving first-line antiretroviral therapy in a multicountry PEPFAR program (RV288) was performed to determine the rates and predictors of virologic suppression. Resistance data from treatment failures are available from Uganda and Nigeria. Each country enrolled 325 subjects into this cross-sectional study. Subjects on first-line therapy were randomly selected for HIV RNA testing (viral load). Regimens included efavirenz or nevirapine with zidovudine/lamivudine or tenofovir/lamivudine. VL was determined from plasma using the Roche COBAS TaqMan HIV-1 Test, High Pure System v1.0 (47 copies/ml). Genotypic resistance testing was performed on samples with VL>1,000 copies/ml. From Uganda, 85% of subjects were undetectable while 7% (23/325) had VL>1,000 copies/ml. The HIV-1 subtype distribution was as follows: A=47.6%, C=14.3%, and D=38.1%. No resistance mutations were found in 14% of subjects. All subjects with resistance had the M184V mutation. Of subjects failing a zidovudine regimen less than 1 year, 88% (7/8) had no thymidine analogue mutations (TAMs), compared to 50% (4/8) failing greater than 1 year. Four subjects (25%) had more than two mutations from the TAM-1 pathway (41L, 210W, 215Y). In Nigeria, 82% were undetectable while 14% (45/325) had VL>1,000 copies/ml. HIV-1 subtype distribution was as follows: 62.8%=CRF02_AG, 34%=pure G, and 2.8%=A. Of the 35 genotyped subjects, 14% (5/35) had no resistance mutations. Of the remainder, 10% (3/30) had no nucleoside analogue mutations while 33% (10/30) had only M184V along with nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations. Forty percent (10/25) of subjects on zidovudine failed without TAMs. Another 25% (5/25) of subjects failing on zidovudine had more than two TAM-1 mutations. Individuals failing first-line antiretroviral therapy (ART) may retain sensitivity to one or more nucleoside analogues from the regimen. Knowledge of drug resistance patterns allow for selection of drugs that can be recycled in future regimens. Accumulation of resistance mutations may compromise future treatment options.
sustiva drug test
Intrapatient variability of drug concentrations over time has not been evaluated as a predictor of drug response but may provide information on the onset and maintenance of response and a patient's adherence to therapy. Our objective was to develop a pharmacologically based measure of intrapatient variability of concentrations and investigate its association with a patient's response to antiretroviral therapy. Efavirenz concentrations were obtained for 50 children enrolled in Pediatric AIDS Clinical Trials Group study 382, a concentration-controlled trial of efavirenz plus nelfinavir and at least one nucleoside reverse transcriptase inhibitor. Efavirenz pharmacokinetic parameters were determined from 24-h concentration-time profiles at weeks 2 and 6 and used to predict trough concentrations obtained during 1 year of therapy. A concentration predictability score, defined as the fraction of measured trough concentrations that fell within a +/-50% range of the predicted concentration, was used to place subjects into high and low concentration predictability groups. Relationships between this score and human immunodeficiency virus RNA levels in plasma were investigated. Eight of 33 children (24%) in the high-predictability group experienced viral rebound, compared with 9 of 17 children (53%) in the low-predictability group (P = 0.042). Children with low predictability scores exhibited a significantly shorter time to their first viral rebounds and were significantly more likely to experience viral rebound; the latter finding persisted after adjustment for baseline viral load and efavirenz exposure at week 6. This novel method for the quantitation of intrapatient concentration variability was independently predictive of virologic rebound. This measure may allow interventions to minimize therapeutic failure and is applicable to other drugs.
Overall, 28 patients receiving a raltegravir-based regimen (4 naive) with tenofovir-emtricitabine (18 cases) or abacavir-lamivudine (10 cases) were included. Mean age was 46.2 years (IQR, 39-52.7), and 79% were male. Median time of HIV was 201.7 months, CD4+ nadir was 268 cells/mm(3), and 75% had previous AIDS. At the diagnosis of neoplasia, 17 were on protease inhibitors and 4 with efavirenz. Ten patients had a non-HIV-related cancer (three breast, two pancreatic, one Ewing sarcoma, one myeloblastic leukemia, one melanoma, one parotid adenocarcinoma, one lung), and 18 had an HIV-related cancer (nine non-Hodgkin lymphoma, seven Hodgkin disease, two anal). Overall, 43% of patients received more than one line of chemotherapy, including antimetabolites in 12 patients (5-FU, capecitabine, methotrexate, gemcitabine), alkylating agents in 12 cases (ciclophosphamide, iphosphamide), vinca alkaloids in 20 patients (vincristine, vinblastine, vindesine), antitumor antibiotics in 16 cases (adriamycin), cisplatin o carboplatin in six and monoclonal antibodies in six patients (rituximab, trastuzumab, cetuximab). Six patients modified the doses of antineoplastic agents due to toxicity (four neutropenia), not related to raltegravir. During a median follow up of 12.7 patients-year in concomitant therapy, there was only 1 case of virological failure and no patient discontinued raltegravir. Plasma concentrations of raltegravir in eight patients showed a median concentration of 143 ng/mL (79-455). Four patients (14%) died during the study, not related to AIDS progression. Raltegravir was continued after chemotherapy in all the cases.
To describe the spectrum of central nervous system (CNS) disease during the first year of antiretroviral therapy (ART) and to determine the contribution of neurological immune reconstitution inflammatory syndrome (IRIS).
sustiva tab 600mg
A5224s was a substudy of A5202, in which HIV-infected treatment-naive participants were randomized and blinded to receive ABC-3TC or TDF-FTC with open-label EFV or ATV/r. Primary bone end points included Dual-emission X-ray absorbtiometry (DXA)-measured percent changes in spine and hip BMD at week 96. Primary analyses were intent-to-treat. Statistical tests used the factorial design and included linear regression, 2-sample t, log-rank, and Fisher's exact tests.
sustiva drug interactions
The objectives of this study were to determine the rate of viral success in HIV-infected patients on first-line ART by the assessment of dried blood spot (DBS) viral load (VL) and to assess the performance of DBS sampling for VL measurement, genotypic resistance and antiretroviral concentration determinations.
is sustiva generic
Breast enlargement was assessed in consecutively evaluated HIV-infected men, and gynecomastia was subsequently confirmed with sonography. For each patient with breast enlargement, a randomly selected control subject without breast enlargement was studied. Clinical data were obtained, including age, body mass index, clinically evident lipodystrophy, prior symptomatic hyperlactatemia, current antiretroviral therapy and duration of exposure to each antiretroviral drug, history of injection drug use, and serological status regarding hepatitis B and hepatitis C. Laboratory parameters, including plasma HIV-1 RNA load, CD4 cell count, free testosterone index, and levels of fasting triglycerides, cholesterol, prolactin, total testosterone, sex hormone-binding globulin, 17-beta-estradiol, follicle-stimulating hormone, luteinizing hormone, and thyroid-stimulating hormone, were measured.
cost of sustiva
Although HIV-associated neurocognitive disorders should be treated with highly active antiretroviral treatment (HAART) regimens with good central nervous system (CNS) penetration, the definition of neuroactive HAART remains controversial. We compared 2 ranking systems to measure HAART neuroeffectiveness.
sustiva generic name
We recorded a high prevalence of toxic effects attributed to antiretroviral treatment for HIV-1. Such data provides a reference for regimen-specific and compound-specific adverse events and could be useful in postmarketing analyses of toxic effects.
The non-nucleoside reverse transcriptase inhibitor efavirenz is a widely prescribed antiretroviral drug used in combined antiretroviral therapy. Despite being an essential and life-saving medication, the required lifelong use of HIV drugs has been associated with a variety of adverse effects, including disturbances in lipid metabolism and increased cardiovascular risk. Efavirenz belongs to those HIV drugs for which cardiovascular and endothelial dysfunctions have been reported. It is here shown that elevated concentrations of efavirenz can inhibit endothelial meshwork formation on extracellular matrix gels by normal and immortalized human umbilical vein cells. This inhibition was associated with an increase in oxidative stress markers, endoplasmic reticulum (ER) stress markers, and autophagy. Induction of ER stress occurred at pharmacologically relevant concentrations of efavirenz and resulted in reduced proliferation and cell viability of endothelial cells, which worsened in the presence of elevated efavirenz concentrations. In combination with the HIV protease inhibitor nelfinavir, both oxidative stress and ER stress became elevated in endothelial cells. These data indicate that pharmacologically relevant concentrations of efavirenz can impair cell viability of endothelial cells and that these effects may be aggravated by either elevated concentrations of efavirenz or by a combined use of efavirenz with other oxidative stress-inducing medications.
The expanded access program to ART in a public, comprehensive AIDS care center in Chile has been highly successful in reaching high undetectability (75%), reducing mortality and improving immune status despite very advanced baseline disease.
A total of 64 subjects (86% male, 66% white, mean [sd] CD4(+) T-cell count 537.3 [191.5]/mm(3)) were analysed. After adjustment for baseline 25(OH)D and demographics, at week 48 DRV/r monotherapy was associated with a +3.6 (95% CI 0.6, 6.6) ng/ml increase in 25(OH)D compared to TDF/FTC/EFV (P=0.02). DRV/r monotherapy was associated with an increase in BMD (+2.9% versus -0.003% at the neck of femur and +2.6% versus +0.008% at the lumbar spine for DRV/r versus TDF/FTC/EFV; P<0.05 for all) and reductions in bone biomarkers compared with those remaining on TDF/FTC/EFV. No significant difference in renal tubular function was observed. Reasons for discontinuation in the DRV/r arm included side effects (n=4) and viral load rebound (n=3), all of which resolved with DRV/r discontinuation or regimen intensification.
Previously, we observed that the oxazinone ring is important for cytochrome P450 2B6 (CYP2B6) activity toward efavirenz ((4S)-6-chloro-4-(2-cyclopropylethynyl)-1,4-dihydro-4-(trifluoromethyl)-2H-3,1-benzoxazin-2-one), a CYP2B6 substrate used to treat HIV. To further understand the structural characteristics of efavirenz that render it a CYP2B6 substrate, we tested the importance of each heteroatom of the oxazinone ring. We assembled a panel of five analogues: 6-chloro-4-(2-cyclopropylethynyl)-1,4-dihydro-2-methyl-4-(trifluoromethyl)-2H-3,1-benzoxazine (1), (4S)-6-chloro-4-[(1E)-2-cyclopropylethenyl]-3,4-dihydro-4-(trifluoromethyl)-2(1H)-quinazolinone (2), (4S)-6-chloro-4-(2-cyclopropylethynyl)-3,4-dihydro-4-(trifluoromethyl)-2(1H)-quinazolinone (3), 6-chloro-4-(cyclopropylethynyl)-3,4-dihydro-4-(trifluoromethyl)-2(1H)-quinolinone (4), and 6-chloro-4-(cyclopropylethynyl)-4-(trifluoromethyl)-4H-benzo[d][1,3]dioxin-2-one (5). The metabolism of compounds 1-5 was investigated using human liver microsomes, individual P450s, and mass spectrometry or UV/Vis absorbance detection. Steady-state analysis of CYP2B6 metabolism of 1-5 showed KM values ranging from 0.3- to 3.9-fold different from that observed for efavirenz (KM : 3.6±1.7 μm). The lowest KM values, approximating 1 μm, were observed for the metabolism of 1, whereas the greatest KM value, 14±6.4 μm, was found for 4. Our work reveals that analogues with heteroatom changes in the oxazinone ring are still CYP2B6 substrates, although the changes in KM suggest altered substrate binding.
PubMed, EMbase, Ovid, Web of Science, Science Direct, and related websites were screened from establishment until July 2013, and scientific meeting proceedings were manually searched. Two reviewers independently screened 118 citations repeatedly to identify randomized controlled trials comparing the efficacy and safety of DTG-based regimen with those of RAL- or elvitegravir-based regimens. Using the selected studies with comparable outcome measures and indications, we performed a meta-analysis based on modified intention-to-treat (mITT), on-treatment (OT), and as-treated (AT) virological outcome data. Independent data extraction and quality assessment were conducted.
The aim of this study was to characterise the population pharmacokinetics of efavirenz in a representative patient population and to identify patient characteristics influencing the pharmacokinetics of efavirenz, with the ultimate goal of further developing techniques that can be applied to optimise therapeutic drug monitoring of antiretroviral agents.
Compounds that can block the CXCR4 chemokine receptor are a promising new class of antiretroviral agents. In these experiments we studied the effect of a modified form of the native stromal cell-derived factor-1 (SDF-1), Met-SDF-1beta. The in vitro susceptibility of two different CXCR4-tropic HIV-1 strains was determined. Antiviral effect was assessed by the reduction of p24 antigen production in PHA-stimulated peripheral blood mononuclear cells with exposure to the modified SDF-1 molecule. The 50% inhibitory concentrations (IC50) were derived from six separate experiments. The IC50 against the two HIV-1 isolates was in 1.0-2.8 microg/ml range for Met-SDF-1beta. Met-SDF-1beta showed synergy to additivity with either zidovudine or nelfinavir at IC75 IC90 and IC95. Additivity was seen when Met-SDF-1beta was combined with efavirenz. No cellular toxicity was observed at the highest concentrations when these agents were used either singly or in combination. This compound is a promising new candidate in a receptor-based approach to HIV-1 infection in conjunction with currently available combination antiretroviral drug therapies.
sustiva renal dosing
The efavirenz, a non nucleoside reverse transcriptase inhibitor of HIV-1, presents a marked pharmacokinetics variability related to an intense hepatic metabolism. Efavirenz is also a potent inducer. Central nervous system (CNS) toxicity associated with efavirenz therapy is a major cause of non adherence and therefore treatment failure. The literature has been analyzed to evaluate the level of evidence of the interest of a therapeutic drug monitoring for efavirenz. Several studies have reported that an efavirenz plasma concentration >1 000 ng/mL is a predictive factor of the viral response. Efavirenz plasma concentrations >4 000 ng/mL were associated to an increase frequency of CNS side effects. CNS toxicity was also more frequent in patients carrying the 516G > T mutation (CYP2B6*6 allele), associated with a significantly greater efavirenz plasma exposure. Non-randomized studies have reported the interest of efavirenz therapeutic drug monitoring to optimize viral response and prevent CNS toxicity, allowing to suggest a level of evidence "recommended" for efavirenz.
sustiva 600 mg
HIV infection and antiretroviral therapy (ART) may create unique risk factors for vitamin D insufficiency, including alterations of vitamin D metabolism by ART. We prospectively compared demographic and clinical parameters between vitamin D sufficient and insufficient HIV-infected (HIV+) adults, and assessed changes in these parameters among insufficient participants following standardized vitamin D supplementation.
sustiva drug class
Forty-seven women and 25 children were studied. Mothers were administered during pregnancy a combination of tenofovir, lamivudine and efavirenz and continued it during breastfeeding (up to 2 years) and thereafter. Drug concentrations were evaluated in mothers (plasma and breast milk) at 1 and 12 months post-partum and in infants (plasma) at 6 and 12 months of age. Drug concentrations were determined using an LC-MS/MS validated methodology.
The combination of tenofovir and efavirenz with either lamivudine or emtricitabine (TELE) has proved to be highly effective in clinical trials for first-line treatment of HIV-1 infection. However, limited data are available on its efficacy in routine clinical practice.
sustiva and alcohol
Samples obtained at the time of HIV seroconversion (1998-2003) were analyzed using the GeneSeq HIV and PhenoSense HIV assays (Monogram Biosciences, Inc., South San Francisco, California, USA).
Nevirapine used in single doses to prevent mother-to-child transmission has been shown to be associated with the development of transient resistant mutations. Here we describe the presence of V106M in seven out of 141 South African women (5%) 6 weeks after receiving nevirapine. V106M is a novel resistance mutation found in subtype C viruses exposed to efavirenz. This mutation is thus also induced at a low frequency in subtype C viruses exposed to single dose nevirapine.