Either Efavirenz Research Articles

CNS Considerations in ART Simplification Strategies.

This review summarizes current knowledge on central nervous system (CNS) considerations in ART simplification strategies. Antiretroviral therapies (ART) showing efficacy in plasma will usually show efficacy in the cerebrospinal fluid (CSF). ART simplification may virologically fail if the new regimen has less than two active drugs, the genetic barrier of drugs is not high, and the patient may harbour archived resistance. Dual therapies including a boosted protease inhibitor (PI) or dolutegravir (DTG) are generally effective from the CNS perspective. In cases of related neurotoxicity, switching from either efavirenz (EFV) or DTG to another equally effective drug with better CNS tolerability usually leads to complete resolution of CNS symptoms. However, improvement may be incomplete when factors other than ART that cannot be easily modified are involved.

Enhancing current human immunodeficiency virus/hepatitis B and human immunodeficiency virus/hepatitis C virus co-infection management.

Enhancing current human immunodeficiency virus/hepatitis B and human immunodeficiency virus/hepatitis C virus co-infection management.

Measuring Adherence to Antiretroviral Therapy via Hair Concentrations in India.

Objective adherence measures are of increasing interest in antiretroviral treatment (ART) monitoring. Hair ART levels predict virologic suppression, and hair is easy to collect and store. No previous study has examined hair levels in an India-based cohort or laboratory. Small hair samples were collected from HIV-positive participants on either efavirenz (EFV)-based or nevirapine (NVP)-based ART in a South India-based study. Hair samples were split and analyzed for EFV or NVP in the University of California, San Francisco -based Hair Analytical Laboratory and the analytic laboratory of the Division of Nutrition at St. John's Research Institute, Bangalore, India, using liquid chromatography/tandem mass spectrometry. Agreement (using Bland-Altman methods) and rank correlation between the 2 laboratories' hair levels were calculated. Rank correlation between self-reported adherence (SRA) over the previous month using a visual analog scale and hair ART levels was calculated. Among 75 participants (38 on NVP; 37 on EFV), the correlation between NVP levels generated by the 2 laboratories was 0.66 (P < 0.0001) and between EFV levels was 0.87 (P < 0.0001). Measurements from St. John's Research Institute were usually within 20% of those from the University of California, San Francisco Hair Analytical Laboratory. SRA was essentially uncorrelated with hair antiretroviral levels for either drug (all correlations < 0.04). Hair levels showed variability in adherence although SRA was >85% in all participants. Hair ART levels measured by both an India-based laboratory and the standard U.S.-based laboratory showed generally high agreement and correlation, demonstrating local capacity. As in many other cohorts, hair ART levels and SRA were not well-correlated, likely indicating limitations in self-report and the need for objective adherence monitoring in resource-limited settings.

Risk factors and co-morbidities associated with changes in renal function among antiretroviral treatment-naïve adults in South Africa: A chart review.

IntroductionOur systematic scoping review has demonstrated a research gap in antiretroviral treatment (ART) nephrotoxicity as well as in the long-term outcomes of renal function for patients on ART in South Africa. Bearing in mind the high prevalence of human immunodeficiency virus (HIV) in South Africa, this is of great concern.ObjectivesTo determine the risk factors and co-morbidities associated with changes in renal function in HIV-infected adults in South Africa.MethodsWe conducted a retrospective study of 350 ART-naïve adult patients attending the King Edward VIII HIV clinic, Durban, South Africa. Data were collected at baseline (pre-ART) and at six, 12, 18 and 24 months on ART. Renal function was assessed in the 24-month period using the Modification of Diet in Renal Disease equation and was categorised into normal renal function (estimated glomerular filtration rate [eGFR] ≥ 60), moderate renal impairment (eGFR 30–59), severe renal impairment (eGFR 15–29) and kidney failure (eGFR < 15 mL/min/1.73 m2). Generalised linear models for binary data were used to model the probability of renal impairment over the five time periods, controlling for repeated measures within participants over time. Risk ratios and 95% confidence intervals (CI) were reported for each time point versus baseline.ResultsThe cohort was 64% female, and 99% were Black. The median age was 36 years. At baseline, 10 patients had hypertension (HPT), six had diabetes, 61 were co-infected with tuberculosis (TB) and 157 patients had a high body mass index (BMI) with 25.4% being categorised as overweight and 19.4% as obese. The majority of the patients (59.3%) were normotensive. At baseline, the majority of the patients (90.4%) had normal renal function (95% CI: 86% – 93%), 7.0% (CI: 5% – 10%) had moderate renal impairment, 1.3% (CI: 0% – 3%) had severe renal impairment and 1.3% (CI: 0% – 3%) had renal failure. As BMI increased by one unit, the risk of renal impairment increased by 1.06 (CI: 1.03–1.10) times. The association of HPT with abnormal renal function was found to be insignificant, p > 0.05. The vast majority of patients were initiated on tenofovir disoproxil fumarate (TDF) (90.6%), in combination with lamivudine (3TC) (100%) and either efavirenz (EFV) (56.6%) or nevirapine (NVP) (43.4%).ConclusionThis study reports a low prevalence of baseline renal impairment in HIV-infected ART-naïve outpatients. An improvement in renal function after the commencement of ART has been demonstrated in this population. However, the long-term outcomes of patients with HIV-related renal disease are not known.

Early upper digestive tract side effects of zidovudine with tenofovir plus emtricitabine in West African adults with high CD4 counts

IntroductionTenofovir (TDF) with emtricitabine (FTC) and zidovudine (ZDV) is a recognized alternate first-line antiretroviral (ART) regimen for patients who cannot start treatment with non-nucleoside reverse transcriptase inhibitors (NNRTIs). Clinical studies comparing TDF+FTC+ZDV to other regimens are lacking.MethodsParticipants in a trial of early ART in Côte d'Ivoire (Temprano ANRS 12136) started treatment with TDF/FTC plus either efavirenz (EFV) or ZDV (HIV-1+2 dually infected patients and women refusing contraception or previously treated with nevirapine). We compared rates of upper digestive serious adverse events (sAEs) between TDF/FTC+EFV and TDF/FTC+ZDV patients during the first six months of treatment. sAEs were defined as either grade 3–4 AEs or persistent grade 1–2 AEs leading to drug discontinuation.ResultsA total of 197 patients (76% women, median CD4 count 395/mm3) started therapy with TDF/FTC, 126 with EFV and 71 with ZDV. During the first six months of ART, 94 patients had digestive AEs (nausea/vomiting) of any grade (EFV 36/126, 29%; ZDV 58/71, 82%, p<0.0001), including 20 sAEs (EFV 3/126, 5%; ZDV 17/71, 24%, p<0.0001). In-patients on TDF/FTC+ZDV with digestive AEs, the median time to the first symptom was two days (IQR: 1–4). Plasma ZDV (Cmax) distributions and pill ZDV dosages were normal. Patients with digestive AEs had higher haemoglobin levels and tended to have higher body mass indices and more frequent past histories of cotrimoxazole (CTX) prophylaxis.ConclusionsWe observed an unexpectedly high rate of digestive sAEs in West African adults, mostly women, who started a 3-nuc ART with TDF/FTC+ZDV in Côte d'Ivoire. These adults were participating in a trial of early ART and had much higher CD4 counts than those who currently routinely start ART in sub-Saharan Africa. They all received CTX concomitantly with ZDV. We suggest that further early prescriptions of TDF+XTC+ZDV should be carefully monitored and that whenever possible, the rate of early upper digestive adverse events should be compared to that occurring in-patients taking other drug regimens. Clinical Trial Number: NCT00495651.

Efavirenz Outperforms Boosted Atazanavir among Treatment-Naive HIV-1-Infected Persons in Routine Clinical Care

Effectiveness of antiretroviral therapy (ART) in a routine clinical care may result different from the clinical trials. We assessed the virologic outcomes in treatment-naive persons who received either efavirenz (EFV) or atazanavir/ritonavir (ATV/r) with a backbone of tenofovir/emtricitabine (TDF/FTC) as their combination ART (cART). This was a retrospective cohort study conducted at the Washington University HIV Outpatient Clinic from January 2004 to June 2009. Predictors of virologic suppression (HIV RNA level <400 copies/mL) by week 48 were assessed by multivariate Cox proportional hazards regression models. Of 324 persons, 221(68%) received EFV and 103 (32%) received ATV/r. Persons on EFV had 1.4-fold increased likelihood of virologic suppression (95% confidence interval, 1.0-1.8) when compared to ATV/r after adjustment with primary drug resistance, pre-cART opportunistic infection, HIV RNA levels, and timing to start cART. In routine clinical care settings, EFV had higher likelihood of achieving virologic suppression than ATV/r with backbone of TDF/FTC.

Safety and effectiveness of efavirenz versus nevirapine-based regimens in resource-limited settings

639–641Keywords: efavirenz, effectiveness, modelling, nevirapine, safety,sub-Saharan AfricaCombination antiretroviral therapy (ART) with eitherefavirenz (EFV) or nevirapine (NVP), both nonnucleo-side reverse transcriptase inhibitors (NNRTIs), and twonucleoside reverse transcriptase inhibitors (NRTI) isrecommended by the WHO as first-line therapy inresource-limited countries [1]. Compared with NVP,EFV is easier to monitor, is relatively well tolerated, hasless frequent and less severe rash and hepatic toxicity thanNVP, and can be administered once daily. Whereas NVPandEFVhavegenerallycomparableclinicalandvirologicefficacy [2–5], because of lower drug–drug interactions,EFV-based ART is associated with superior virologicoutcome compared with NVP-based ART in individualswith tuberculosis (TB) receiving anti-TB therapycontaining rifampicin. Therefore, efavirenz is theNNRTI antiretroviral drug of choice of TB-coinfectedindividuals [6–9]. However, there have been concernsregarding potential for central nervous system birthdefects with first-trimester exposure to EFV based onstudiesinpregnantrhesusmacaquesandretrospectivecasereportsinhumansthathavelimitedEFVuseinwomenofchildbearing age. This is a problem in many resource-limitedsettings,wherewomenconstitute50%or moreofHIV-infected individuals and TB is endemic, but there islimited access to contraception or women may wish tobecome pregnant.In this issue, Ouattara and colleagues use a computersimulation model to evaluate the risks and benefits ofusing EFV and NVP in women of childbearing age inresource-limited countries [10]. Using the previouslyvalidated Cost-Effectiveness of Preventing AIDS Com-plications (CEPAC) International model, the authorssimulated the trade-off between potential excess birthdefects and potential long-term clinical benefits forwomen starting EFV-based versus NVP-based ART inCote d’Ivoire. In a ‘hypothetical’ cohort of 100000women starting ARTwith EFV, the authors found that adrug with lower toxicity and requiring less regimenswitching led to approximately 911 more women aliveafter 10 years compared with those starting with NVP, animprovement in survival of approximately 1%. However,over thesameperiod,therewere59morebirthdefectsinwomen initiating EFV-based ART than those startingwith NVP. The authors concluded that in Cote d’Ivoire,initiating ART with EFV instead of NVP is likely to

Resistance profiles of emtricitabine and lamivudine in tenofovir-containing regimens

To compare the frequency of the selection of the M184V/I resistance mutation in HIV-infected patients who experienced virological failure while receiving emtricitabine (FTC) or lamivudine (3TC), administered with tenofovir disoproxil fumarate (TDF) and either efavirenz (EFV) or a ritonavir-boosted protease inhibitor (PI; lopinavir or atazanavir). Patient data held at two clinical centres in France were analysed retrospectively. Eligible patients had experienced virological suppression (plasma HIV RNA <200 copies/mL) for ≥ 6 months before experiencing their first virological failure (at least two measurements of plasma HIV RNA ≥ 200 copies/mL). Of the 880 patients eligible for the study, 278 patients had experienced virological failure while receiving FTC + TDF + ritonavir-boosted PI, 257 while receiving FTC + TDF + EFV, 178 while receiving 3TC + TDF + EFV and 167 while receiving 3TC + TDF + ritonavir-boosted PI. Proportions of patients harbouring the M184V/I mutation were 24% (n = 62) for those who received FTC + TDF + EFV versus 51% (n = 91) for 3TC + TDF + EFV (P < 0.0001; Fisher's exact test); proportions were 11% (n = 30) for FTC + TDF + ritonavir-boosted PI versus 22% (n = 37) for 3TC + TDF + ritonavir-boosted PI (P = 0.002; Fisher's exact test). The use of lamivudine versus emtricitabine (P = 0.001), non-nucleoside reverse transcriptase inhibitors versus ritonavir-boosted PIs (P = 0.01) and the level of viral load at the time of virological failure (P = 0.01) were associated with selection of the M184V/I mutation (logistic regression analysis). Emtricitabine and lamivudine showed differing resistance profiles when administered in combination with tenofovir disproxil fumarate and either efavirenz or a ritonavir-boosted PI. The prevalence of the M184V/I resistance mutation was significantly lower in patients who received emtricitabine and tenofovir disoproxil fumarate than in those who received lamivudine and tenofovir disoproxil fumarate.

Aminotransferase Serum Levels Decrease after Initiating Antiretroviral Treatment in HIV Infected Patients

To evaluate the effect of antiretroviral treatment on aminotransferase serum levels in treatment-naïve patients infected with human immunodeficiency virus (HIV). We conducted a longitudinal study in treatment-nanaïve patients infected with HIV. Patients were excluded if they had consumed alcohol during the last three months or had an opportunistic disease or co-infection. All 54 enrolled patients were evaluated and those having a CD4+ cell count <350 cells/ml (41/54) were allocated to the treatment group (TG), while those with CD4+ counts >350 cells/ml (13/54) did not receive any anti-retroviral treatment (ART). TG patients received either efavirenz (EFV) (21/41) or lopinavir/ritonavir (LPV/RTV) (20/41), each with zidovudine/lamivudine (ZDV/LMV). During the trial, 2 subjects in the EFV group were excluded due to rash and 1 subject in the LPV/RTV group due to gastric intolerance. The remaining 51 subjects (13 (25.5%) in the NTG and 38 (74.5%) in the TG) were included in the data analysis. Overall, 43 (84%) of analyzed patients were male and 8 (16%) female with an overall mean age of 33 ± 9 years. Of the 38 treated patients, 19 received LPV/RTV and 19 received EFV. Patients in the TG showed an increase in their CD4+ cell count, a decrease in aspartate aminotransferase (AST) from 39.3 ± 28 IU/ml to 22.7 ± 6 IU/ml (p = 0.02), and a decrease in alanine aminotransferase (ALT) from 52.0 ± 25 IU/ml to 23.8 ± 13 IU/ml (p < 0.01). Patients in the NTG showed no statistically significant differences in these measurements. Positive correlation was found between HIV viral load, AST (r = 0.31, p = 0.001) and ALT (r = 0.40, p = 0.04). There is a significant decrease in aminotransferase serum levels following the initiation of antiretroviral treatment in HIV infected patients.

Observational Study to Evaluate Clinical Outcomes After First-Line Efavirenz-or Lopinavir-Ritonavir-Based HAART in Treatment-Naive Patients

To evaluate clinical, immunological, and virological outcomes after first-line highly active antiretroviral therapy (HAART) with a regimen including either efavirenz (EFV) or lopinavir/ritonavir (LPV/r) in treatment-naive adult patients in routine clinical care. An ongoing prospective, observational follow-up study included all patients starting their first antiretroviral therapy (ART) with any of the studied regimens from July 1998 to July 2004. The follow-up period was finalized in September 2006, when all patients completed an observation of at least 96 weeks. Mortality rates, CD4 counts, viral suppression (HIV RNA below 50 copies/mL), and discontinuation of any component of the regimen were compared at 48 and 96 weeks. Despite the worst immunological status of the LPV/r group patients at baseline, this regimen was at least as effective as the one based on EFV not only in terms of treatment durability but also in terms of virological responses, nevertheless with an apparently quicker immune recovery. In general terms, both regimens present similar tolerability and safety outcomes except for the higher risk of increasing triglyceride (TG) levels in the LPV/r group. Low durability was observed in both regimens. In a routine clinical care setting, initial HAART containing LPV/r seems to present an effectiveness, tolerability, and toxicity similar to the one containing EFV.

Comparison of Neuropsychiatric Side Effects in an Observational Cohort of Efavirenz- and Protease Inhibitor-Treated Patients

Purpose: To compare the extent of neuropsychiatric disturbances in two similar groups of HIV-infected patients treated for >4 weeks with either efavirenz (EFV) or protease inhibitors (PIs) as part of their antiretroviral therapy (ART). Method: A cross-sectional, questionnaire-based cohort of HIV patients who received two nucleoside reverse transcriptase inhibitors combined with either EFV (n = 75) or one or more PIs (n = 77) for at least 4 weeks and were tolerating therapy. The extent of neuropsychiatric disturbances was evaluated based on self-reported symptoms using the psychological evaluation test SCL-90-R. Treatment duration was broken down into quartiles of 30-198 days, >198-365 days, >365-637 days, and >637 days. Results: In the first 6 months of therapy, significantly higher (worse) scores were seen in 39/75 (52%) of the patients receiving EFV. The EFV-treated group had significantly higher scores for somatization, anxiety, obsessive-compulsive behavior, the Global Severity Index, and the Positive Symptom Distress Index, with trends for higher scores in paranoid ideation and depression symptom subcategories. Over the following 6 to 12 months of therapy, the EFV group scored higher than the PI group in somatization, anxiety, obsessive-compulsive behavior, hostility, depression, the Global Severity Index, and the Positive Symptom Total, but the differences were not significant. After 12 months of therapy, the EFV group had significantly lower scores than the PI group for somatization, interpersonal sensitivity, Global Severity Index, and Positive Symptom Total. Conclusion: EFV-induced neuropsychiatric symptoms can last up to 200 days after treatment initiation. However, symptom severity appears to decline over time in EFV-treated patients versus patients treated with a PI-based ART.

Comparison of Neuropsychiatric Side Effects in an Observational Cohort of Efavirenz- and Protease Inhibitor-Treated Patients

Purpose: To compare the extent of neuropsychiatric disturbances in two similar groups of HIV-infected patients treated for >4 weeks with either efavirenz (EFV) or protease inhibitors (PIs) as part of their antiretroviral therapy (ART). Method: A cross-sectional, questionnaire-based cohort of HIV patients who received two nucleoside reverse transcriptase inhibitors combined with either EFV (n = 75) or one or more PIs (n = 77) for at least 4 weeks and were tolerating therapy. The extent of neuropsychiatric disturbances was evaluated based on self-reported symptoms using the psychological evaluation test SCL-90-R. Treatment duration was broken down into quartiles of 30-198 days, >198-365 days, >365-637 days, and >637 days. Results: In the first 6 months of therapy, significantly higher (worse) scores were seen in 39/75 (52%) of the patients receiving EFV. The EFV-treated group had significantly higher scores for somatization, anxiety, obsessive-compulsive behavior, the Global Severity Index, and the Positive Symptom Distress Index, with trends for higher scores in paranoid ideation and depression symptom subcategories. Over the following 6 to 12 months of therapy, the EFV group scored higher than the PI group in somatization, anxiety, obsessive-compulsive behavior, hostility, depression, the Global Severity Index, and the Positive Symptom Total, but the differences were not significant. After 12 months of therapy, the EFV group had significantly lower scores than the PI group for somatization, interpersonal sensitivity, Global Severity Index, and Positive Symptom Total. Conclusion: EFV-induced neuropsychiatric symptoms can last up to 200 days after treatment initiation. However, symptom severity appears to decline over time in EFV-treated patients versus patients treated with a PI-based ART.

Therapeutic Effects of Nonnucleoside Reverse Transcriptase Inhibitors on the Central Nervous System in HIV-1–Infected Patients

Summary: Psychomotor slowing predicts the development of HIV-1-associated dementia, AIDS, and death independent of immune status. We retrospectively selected all patients who showed pathologic psychomotor slowing as a sign of central nervous system (CNS) dysfunction before the onset of therapy and who were then treated with nonnucleoside reverse-transcriptase inhibitors—either efavirenz (EFV) (n = 65 patients) or nevirapine (NVP) (n = 39 patients), each given in combination with two nucleoside analogues (NAs). Patients who were treated only with two NAs (n = 66) served as controls. Patients were observed for 6 months. Both EFV and NVP combinations improved CNS function as determined by electrophysiologic motor tests. The therapeutic effects of EFV and NVP did not depend on the type of NA added. Although results did not reach significance, NVP combinations were more effective than EFV combinations or therapy regimens with NAs alone in patients who were naive to all antiretroviral therapy. EFV and NVP combinations were equally effective in patients pretreated with highly active antiretroviral therapy, including protease inhibitors.