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AIDS and Behavior Feb 2017Poor adherence remains a major barrier to achieving the clinical and public health benefits of antiretroviral drugs (ARVs). A systematic review and qualitative... (Review)
Review
Poor adherence remains a major barrier to achieving the clinical and public health benefits of antiretroviral drugs (ARVs). A systematic review and qualitative meta-synthesis was conduct to evaluate how ARV adverse drug reactions may influence ARV adherence. Thirty-nine articles were identified, and 33 reported that ARV adverse drug reactions decreased adherence and six studies found no influence. Visually noticeable adverse drug reactions and psychological adverse reactions were reported as more likely to cause non-adherence compared to other adverse drug reactions. Six studies reported a range of adverse reactions associated with EFV-containing regimens contributing to decreased adherence. Informing HIV-infected individuals about ARV adverse drug reactions prior to initiation, counselling about coping mechanisms, and experiencing the effectiveness of ARVs on wellbeing may improve ARV adherence.
Topics: Adaptation, Psychological; Alkynes; Anti-HIV Agents; Benzoxazines; Counseling; Cyclopropanes; Drug-Related Side Effects and Adverse Reactions; HIV Infections; Humans; Medication Adherence; Qualitative Research
PubMed: 27613645
DOI: 10.1007/s10461-016-1545-0 -
Expert Review of Anti-infective Therapy 2016Efavirenz is part of the first-line treatment for HIV patients including those in South Africa with approximately 50% experiencing neuropsychiatric side effects. A... (Review)
Review
Efavirenz is part of the first-line treatment for HIV patients including those in South Africa with approximately 50% experiencing neuropsychiatric side effects. A systematic review of papers reporting neuropsychiatric side effects with efavirenz published between January 2001 and December 2014 was performed, to provide guidance. 13 articles were reviewed. Patient ages ranged between 37 to 41 years, with a high percentage males. Scales used to measure incidence and severity of side effects were varied; with disease severity or stage not reported. Patients with psychoses were excluded. Most commonly reported side effects were a reduction in sleep quality, depression, dizziness and anxiety. These were generally mild and not warranting discontinuation of efavirenz. It is difficult to directly compare the studies. Standardised methods need to be introduced and all patient groups represented including the elderly, children, patients with active symptomatic illness and more women especially among the African population.
Topics: Alkynes; Anti-HIV Agents; Anxiety; Benzoxazines; Cyclopropanes; Depression; Dizziness; HIV Infections; Humans; Sleep Wake Disorders
PubMed: 26900637
DOI: 10.1586/14787210.2016.1157469 -
BMC Infectious Diseases Oct 2015Abacavir is one of the recommended nucleoside reverse transcriptase inhibitors (NRTIs) for the treatment of HIV infections among children and adolescents. However, there... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of abacavir-containing combination antiretroviral therapy as first-line treatment of HIV infected children and adolescents: a systematic review and meta-analysis.
BACKGROUND
Abacavir is one of the recommended nucleoside reverse transcriptase inhibitors (NRTIs) for the treatment of HIV infections among children and adolescents. However, there are concerns that the antiviral efficacy of abacavir might be low when compared to other NRTIs especially among children. There are also concerns that abacavir use may lead to serious adverse events such as hypersensitivity reactions and has potential predisposition to developing cardiovascular diseases
METHODS
We searched four electronic databases, four conference proceedings and two clinical trial registries in August 2014, without language restrictions. Experimental and observational studies with control groups that examined the efficacy and safety of abacavir-containing regimens in comparison with other NRTIs as first-line treatment for HIV-infected children and adolescents aged between one month and eighteen years were eligible. Two authors independently screened search results, extracted data and assessed the risk of bias of included studies using a pre-specified, standardised data extraction form and validated risk of bias tools. We also assessed the quality of evidence per outcome with the GRADE tool.
RESULTS
We included two randomised controlled trials (RCTs) and two analytical cohort studies with a total of 10,595 participants. Among the RCTs we detected no difference in virologic suppression after a mean duration of 48 weeks between abacavir- and stavudine-containing regimens (2 trials; n = 326: RR 1.28; 95 % CI 0.67-2.42) with significant heterogeneity (P = 0.02; I(2) = 81 %). We also found no significant differences between the two groups for adverse events and death. After five years of follow-up, virologic suppression improved with abacavir (1 trial; n = 69: RR 1.96; 95 % CI 1.11-3.44). For cohort studies, we detected that the virologic suppression activity of abacavir was less effective than stavudine in both the lopinavir/ritonavir (1 study, n = 2165: RR 0.79, 95 % CI 0.67-0.92) and efavirenz sub-groups (1 study, n = 3204: RR 0.79, 95 % CI 0.67-0.92) respectively. The quality of evidence from RCTs was moderate for virologic suppression but low for death and adverse events, while that of cohort studies was low for all three these outcomes.
CONCLUSIONS
Available evidence showed little or no difference between abacavir-containing regimen and other NRTIs regarding efficacy and safety when given to children and adolescents as a first-line antiretroviral therapy.
Topics: Adolescent; Alkynes; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Benzoxazines; Child; Child, Preschool; Cohort Studies; Cyclopropanes; Dideoxynucleosides; Drug Therapy, Combination; Female; HIV Infections; Humans; Infant; Lopinavir; Male; Ritonavir; Stavudine
PubMed: 26502899
DOI: 10.1186/s12879-015-1183-6 -
PloS One 2015Efavirenz, a non-nucleoside reverse-transcriptase inhibitor (NNRTI) is one of the most commonly prescribed antiretroviral drugs. The present article provides a... (Meta-Analysis)
Meta-Analysis Review
Efavirenz, a non-nucleoside reverse-transcriptase inhibitor (NNRTI) is one of the most commonly prescribed antiretroviral drugs. The present article provides a systematic overview and meta-analysis of clinical trials comparing efavirenz and other active drugs currently recommended for treatment of HIV-infected, antiretroviral-naive patients. Electronic databases (Pubmed, Embase, the Cochrane Library, Trip Database) were searched up till 23 December 2013 for randomized controlled clinical trials published as a peer-reviewed papers, and concerning efavirenz-based regimens used as initial treatment for HIV infection. Thirty-four studies were included in the systematic review, while twenty-six trials were suitable for the meta-analysis. Efavirenz was compared with drugs from four different classes: NNRTIs other than efavirenz (nevirapine or rilpivirine), integrase strand transfer inhibitors (InSTIs), ritonavir-boosted protease inhibitors (bPI) and chemokine (C-C motif) receptor 5 (CCR5) antagonists (maraviroc), all of them were added to the background regimen. Results of the current meta-analysis showed that efavirenz-based regimens were equally effective as other recommended regimens based on NNRTI, ritonavir-boosted PI or CCR5 antagonist in terms of efficacy outcomes (disease progression and/or death, plasma viral HIV RNA <50 copies/ml) while statistically significant more patients treated with InSTI achieved plasma viral load <50 copies/ml at week 48. In comparison with both InSTI-based and CCR5-based therapy, efavirenz-based treatment was associated with a higher risk of therapy discontinuation due to adverse events. However, comparisons of efevirenz-based treatment with InSTI-based and CCR5-based therapy were based on a limited number of trials, therefore, conclusions from these two comparisons must be confirmed in further reliable randomized controlled studies. Results of our meta-analysis support the present clinical guidelines for antiretroviral-naive, HIV-infected patients, in which efavirenz is one of the most preferred regimens in the analyzed population. Beneficial safety profile of InSTI-based and CCR5-based therapy over efavirenz-based treatment needs further studies.
Topics: Adult; Alkynes; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Benzoxazines; Cyclopropanes; HIV Infections; HIV Protease Inhibitors; Humans; Randomized Controlled Trials as Topic; Receptors, CCR5; Reverse Transcriptase Inhibitors; Ritonavir; Treatment Outcome
PubMed: 25933004
DOI: 10.1371/journal.pone.0124279 -
Journal of Acquired Immune Deficiency... Aug 2015Efavirenz (EFV) is widely used for the treatment of antiretroviral-naive HIV-positive individuals, but there are concerns about the risk of adverse neuropsychiatric... (Meta-Analysis)
Meta-Analysis Review
Comparative Safety and Neuropsychiatric Adverse Events Associated With Efavirenz Use in First-Line Antiretroviral Therapy: A Systematic Review and Meta-Analysis of Randomized Trials.
INTRODUCTION
Efavirenz (EFV) is widely used for the treatment of antiretroviral-naive HIV-positive individuals, but there are concerns about the risk of adverse neuropsychiatric events. We systematically reviewed the safety of EFV in first-line therapy.
METHODS
Four databases were searched until October 2014 for randomized trials comparing EFV against non-EFV-based regimens for the treatment of antiretroviral-naive HIV-positive adults and children. The primary outcome was drug discontinuation as a result of any adverse event. Relative risks and proportions were pooled using random-effects meta-analysis.
RESULTS
Forty-two trials were included for review. A lower relative and absolute risk of discontinuations due to adverse drug reactions was seen with EFV compared to nevirapine. The relative and absolute risk of discontinuation was greater for EFV compared with low-dose EFV, rilpivirine, tenofovir, atazanavir, and maraviroc. The relative risk of discontinuation was greater for EFV compared with dolutegravir and raltegravir, but absolute risks were not significantly different. There was no difference in the risk of any severe clinical adverse events for any comparison. With the exception of dizziness, fewer than 10% of patients exposed to EFV experienced any other specific type of neuropsychiatric event. No suicides were reported.
CONCLUSIONS
This review found that over 90% of patients remained on an EFV-based first-line regimen after an average follow-up time of 78 weeks. The relative risk of discontinuations due to adverse events was higher for EFV compared with most other first-line options, but absolute differences were less than 5% for all comparisons.
Topics: Alkynes; Anti-HIV Agents; Benzoxazines; Central Nervous System Diseases; Cyclopropanes; HIV Infections; Humans
PubMed: 25850607
DOI: 10.1097/QAI.0000000000000606 -
International Journal of Infectious... Aug 2014Antiretroviral therapy (ART) reduces the morbidity and mortality of patients infected with HIV. Standard ART includes either nevirapine or efavirenz, however the... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Antiretroviral therapy (ART) reduces the morbidity and mortality of patients infected with HIV. Standard ART includes either nevirapine or efavirenz, however the efficacy of these drugs is limited in patients receiving rifampin treatment for tuberculosis (TB). We compared the efficacy and safety of nevirapine- and efavirenz-based ART regimens in patients co-infected with both HIV and TB through a systematic review and meta-analysis.
METHODS
A comprehensive search of the literature was carried out to identify clinical trials comparing the efficacy and safety of nevirapine- and efavirenz-based ART regimens in HIV-associated TB. Eligible clinical studies included at least one primary or secondary event; the primary event was virological response and secondary events were TB treatment outcomes, mortality, and safety profile.
RESULTS
This meta-analysis compared five randomized clinical trials and four retrospective clinical trials. Both included patients co-infected with HIV and TB; 833 received nevirapine, while 1424 received efavirenz. The proportion of patients achieving a virological response by the end of the follow-up was higher in the efavirenz group: plasma viral load <400 copies/ml, risk ratio (RR) 1.10, 95% confidence interval (CI) 1.03-1.17 (p = 0.004); plasma viral load<50 copies/ml, RR 1.07, 95% CI 0.98-1.16 (p = 0.146). No significant differences were found in either mortality (RR 0.70, 95% CI 0.44-1.13, p = 0.142) or TB treatment outcomes (RR 1.01, 95% CI 0.96-1.06, p = 0.766). Due to adverse advents, nevirapine-based regimens significantly increased the risk of discontinuation of assigned ART (RR 0.43, 95% CI 0.23-0.81, p = 0.009).
CONCLUSIONS
Although efavirenz-based ART was associated with more satisfactory virological outcomes, nevirapine-based ART could be considered an acceptable alternative for patients for whom efavirenz cannot be administered.
Topics: Alkynes; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Antitubercular Agents; Benzoxazines; CD4 Lymphocyte Count; Clinical Trials as Topic; Coinfection; Cyclopropanes; HIV Infections; Humans; Nevirapine; Rifampin; Treatment Outcome; Tuberculosis; Viral Load
PubMed: 24911886
DOI: 10.1016/j.ijid.2014.04.020 -
AIDS (London, England) Mar 2014Primate studies and some observational human data have raised concern regarding an association of first-trimester efavirenz exposure with central nervous system... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Primate studies and some observational human data have raised concern regarding an association of first-trimester efavirenz exposure with central nervous system congenital anomalies. The objective of this review is to update evidence on efavirenz safety in HIV-infected pregnant women to inform revision of the 2013 WHO guidelines for antiretroviral therapy in low and middle-income countries.
DESIGN
A systematic review and meta-analysis.
METHODS
We searched for studies reporting birth outcomes among women exposed to efavirenz during the first trimester of pregnancy up to 10 January 2014. Relative risks of congenital anomalies comparing women exposed to efavirenz and nonefavirenz-based antiretroviral regimens were pooled using random effects meta-analysis.
RESULTS
Twenty-three studies were included in this review, among which 21 reported the birth outcomes of 2026 live births among women exposed to efavirenz during the first trimester of pregnancy. Forty-four congenital anomalies were reported, giving a pooled proportion of 1.63% [95% confidence interval (95% CI) 0.78-2.48], with only one neural tube defect. Twelve studies reported birth outcomes of women exposed to efavirenz or nonefavirenz-containing regimens during the first trimester of pregnancy. Pooled analysis found no differences in overall risks congenital anomalies between these two groups (relative risk 0.78, 95% CI 0.56-1.08). The incidence of neural tube defects was low, 0.05% (95% CI <0.01-0.28), and similar to incidence in the general population.
DISCUSSION
This updated analysis found no evidence of an increased risk of overall or central nervous system congenital anomalies associated with first-trimester exposure to efavirenz, similar to previous systematic reviews. This review contributed to the evidence base for the revised 2013 WHO guidelines on antiretroviral therapy, which recommend that efavirenz can be included as part of first-line therapy in adults regardless of sex, and that it can be used throughout pregnancy, including during the first trimester. However, because of the low incidence of central nervous system anomalies in the overall population and relatively small number of exposures in the current literature, continued birth outcomes prospective surveillance is warranted.
Topics: Abnormalities, Drug-Induced; Alkynes; Benzoxazines; Central Nervous System Diseases; Cyclopropanes; Female; HIV Infections; Humans; Infectious Disease Transmission, Vertical; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Trimester, First; Reverse Transcriptase Inhibitors; Treatment Outcome
PubMed: 24849471
DOI: 10.1097/QAD.0000000000000231 -
PloS One 2013Nevirapine belongs to the group of non-nucleoside reverse transcriptase inhibitors (NNRTIs) and is commonly administered in first-line treatment of HIV infection. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Nevirapine belongs to the group of non-nucleoside reverse transcriptase inhibitors (NNRTIs) and is commonly administered in first-line treatment of HIV infection.
OBJECTIVE
Systematic review and meta-analysis was undertaken to compare effectiveness of nevirapine-based regimens with other antiretroviral schedules used as an initial treatment of HIV-infected antiretroviral-naive subjects.
METHODS
Electronic databases (PubMed, EMBASE, the Cochrane Library, Trip Database) were searched up to 28 December 2012 for randomized controlled trials (RCTs) published as a full text and regarding nevirapine-based regimens used as a initial treatment for HIV infection. Meta-analysis was performed with RevMan(®) V 5.2 software.
RESULTS
Twelve RCTs were included in the systematic review and all of them were suitable for meta-analysis. Results of the meta-analysis have shown that nevirapine, efavirenz, and ritonavir-boosted protease inhibitor, added to the background regimens, were equally effective in terms of reaching undetectable plasma HIV RNA level as well as risk of disease progression or death. Compared with ritonavir-boosted protease inhibitor-based regimens, nevirapine-based regimens statistically significantly increased the risk of discontinuation of assigned treatment (RR=3.10; 95% CI: 1.14-8.41; p<0.05).
CONCLUSIONS
Despite limited RCTs data available for particular comparisons, our results suggest that nevirapine-based regimens may be considered for first-line treatment of HIV-infected adults, due to their comparable efficacy to the other currently recommended initial antiretroviral therapies.
Topics: Alkynes; Anti-HIV Agents; Benzoxazines; Cyclopropanes; Drug Therapy, Combination; HIV Infections; HIV Protease Inhibitors; Humans; Nevirapine; Randomized Controlled Trials as Topic; Ritonavir; Treatment Outcome
PubMed: 24116123
DOI: 10.1371/journal.pone.0076587 -
PloS One 2013There is conflicting evidence and practice regarding the use of the non-nucleoside reverse transcriptase inhibitors (NNRTI) efavirenz (EFV) and nevirapine (NVP) in... (Comparative Study)
Comparative Study Meta-Analysis Review
INTRODUCTION
There is conflicting evidence and practice regarding the use of the non-nucleoside reverse transcriptase inhibitors (NNRTI) efavirenz (EFV) and nevirapine (NVP) in first-line antiretroviral therapy (ART).
METHODS
We systematically reviewed virological outcomes in HIV-1 infected, treatment-naive patients on regimens containing EFV versus NVP from randomised trials and observational cohort studies. Data sources include PubMed, Embase, the Cochrane Central Register of Controlled Trials and conference proceedings of the International AIDS Society, Conference on Retroviruses and Opportunistic Infections, between 1996 to May 2013. Relative risks (RR) and 95% confidence intervals were synthesized using random-effects meta-analysis. Heterogeneity was assessed using the I(2) statistic, and subgroup analyses performed to assess the potential influence of study design, duration of follow up, location, and tuberculosis treatment. Sensitivity analyses explored the potential influence of different dosages of NVP and different viral load thresholds.
RESULTS
Of 5011 citations retrieved, 38 reports of studies comprising 114 391 patients were included for review. EFV was significantly less likely than NVP to lead to virologic failure in both trials (RR 0.85 [0.73-0.99] I(2) = 0%) and observational studies (RR 0.65 [0.59-0.71] I(2) = 54%). EFV was more likely to achieve virologic success than NVP, though marginally significant, in both randomised controlled trials (RR 1.04 [1.00-1.08] I(2) = 0%) and observational studies (RR 1.06 [1.00-1.12] I(2) = 68%).
CONCLUSION
EFV-based first line ART is significantly less likely to lead to virologic failure compared to NVP-based ART. This finding supports the use of EFV as the preferred NNRTI in first-line treatment regimen for HIV treatment, particularly in resource limited settings.
Topics: Alkynes; Benzoxazines; Cyclopropanes; HIV Infections; HIV-1; Humans; Nevirapine; Treatment Outcome; Tuberculosis; Withholding Treatment
PubMed: 23894391
DOI: 10.1371/journal.pone.0068995 -
Expert Opinion on Drug Safety Nov 2013Efavirenz commonly causes early neuropsychiatric side effects, but tolerance develops in most patients. There is emerging evidence that efavirenz use may damage neurons,... (Comparative Study)
Comparative Study Review
INTRODUCTION
Efavirenz commonly causes early neuropsychiatric side effects, but tolerance develops in most patients. There is emerging evidence that efavirenz use may damage neurons, which could result in impaired neurocognitive performance.
AREAS COVERED
The authors conducted a systematic review using the PubMed database, references cited by other articles and conference web sites to determine if there is evidence that efavirenz may contribute to cognitive impairment by damaging nerve cells.
EXPERT OPINION
There is weak clinical evidence suggesting that efavirenz use may worsen neurocognitive impairment or be associated with less improvement in neurocognitive impairment than other antiretrovirals. Efavirenz, especially its major metabolite 8-hydroxy-efavirenz, is toxic in neuron cultures at concentrations found in the cerebrospinal fluid. Extensive metabolizers of efavirenz may therefore be more likely to develop efavirenz toxicity by forming more 8-hydroxy-efavirenz. Several potential mechanisms exist to explain the observed efavirenz neurotoxicity, including altered calcium hemostasis, decreases in brain creatine kinase, mitochondrial damage, increases in brain proinflammatory cytokines and involvement of the cannabinoid system. There is a need for large randomized controlled trials to determine if the neuronal toxicity induced by efavirenz results in clinically significant neurological impairment.
Topics: Alkynes; Animals; Benzoxazines; Brain; Calcium; Cognition Disorders; Cyclopropanes; Drug Tolerance; Humans; Neurons; Neurotoxicity Syndromes; Reverse Transcriptase Inhibitors
PubMed: 23889591
DOI: 10.1517/14740338.2013.823396