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The Journal of Antimicrobial... Sep 2010To compare lipid profiles in HIV-infected adults receiving atazanavir-based regimens. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To compare lipid profiles in HIV-infected adults receiving atazanavir-based regimens.
METHODS
We conducted a systematic review of randomized controlled trials (RCTs) comparing atazanavir or atazanavir/ritonavir with a comparator and evaluated lipids at 48 weeks. We searched MEDLINE, EMBASE, CENTRAL, LILACS, Current Controlled Trials, National Institutes of Health Clinical Trials Registry, trials at AIDSinfo and HIV conference proceedings to May 2009. Standardized mean difference (SMD) between study arms in change from baseline to week 48 in lipid parameters was determined weighted by study size and 95% confidence intervals (CI) were calculated.
RESULTS
Nine eligible RCTs were identified (n = 3346). SMDs (mmol/L) in four RCTs comparing atazanavir/ritonavir with a ritonavir-boosted protease inhibitor were: total cholesterol, -0.62 (95% CI -0.72, -0.51); low-density lipoprotein (LDL) cholesterol, -0.31 (95% CI -0.44, -0.17); high-density lipoprotein (HDL) cholesterol, -0.16 (95% CI -0.27, -0.06); non-HDL cholesterol, -0.58 (95% CI -0.69, -0.48); and triglycerides, -0.46 (95% CI -0.58, -0.34). Atazanavir compared with non-atazanavir (three RCTs) found lower total, LDL and non-HDL cholesterol, and triglycerides [SMD -0.87 mmol/L (95% CI -0.99, -0.76); -0.56 mmol/L (95% CI -0.67, -0.45); -0.88 mmol/L (95% CI -0.99, -0.76); and -0.56 mmol/L (95% CI -0.75, -0.36), respectively], but HDL cholesterol did not differ [-0.16 mmol/L (95% CI -0.49, 0.16)]. In the atazanavir/ritonavir versus atazanavir comparison (two RCTs), total [SMD 0.44 mmol/L (95% CI 0.23, 0.65)] and non-HDL cholesterol [SMD 0.44 mmol/L (95% CI 0.23, 0.65)] were higher, but HDL cholesterol, LDL cholesterol and triglycerides were not different.
CONCLUSIONS
At 48 weeks, plasma lipid concentrations were lower with atazanavir/ritonavir than with other ritonavir-boosted protease inhibitor regimens. Total and non-HDL cholesterol were higher with atazanavir/ritonavir than atazanavir alone.
Topics: Adult; Anti-HIV Agents; Atazanavir Sulfate; HIV Infections; Humans; Lipids; Oligopeptides; Pyridines; Randomized Controlled Trials as Topic; Ritonavir
PubMed: 20554568
DOI: 10.1093/jac/dkq231 -
Archives of Virology Aug 2017Atazanavir (ATZ) is a well-tolerated protease inhibitor that can be boosted with ritonavir (r) to treat infection with resistant strains of human immunodeficiency virus... (Meta-Analysis)
Meta-Analysis Review
Atazanavir (ATZ) is a well-tolerated protease inhibitor that can be boosted with ritonavir (r) to treat infection with resistant strains of human immunodeficiency virus 1 (HIV-1). The aim of this meta-analysis was to compare the efficacy, safety, and metabolic effects of ATZ/r regimen versus commonly used antiretroviral drugs such as lopinavir (LPV) and darunavir (DRV) in HIV-1-infected patients. We searched PubMed, Scopus, Embase and Cochrane CENTRAL, using relevant keywords. Data were extracted from eligible randomized trials and pooled as risk ratios (RR) or standardized mean differences (SMD) in a meta-analysis model using RevMan software. Nine randomized controlled trials (RCTs) (3292 patients) were eligible for the final analysis. After 96 weeks of treatment, the pooled effect estimate did not favor either ATZ/r or LPV/r in terms of virological failure rate (RR 1.11, 95% CI [0.74, 1.66]). However, ATZ/r was marginally superior to LPV/r in terms of increasing the proportion of patients with HIV RNA <50 copies/ml (RR 1.09, 95% CI [1.01, 1.17]). The pooled effect estimate did not favor ATZ/r over DRV/r regarding the change in plasma levels of total cholesterol, triglycerides, or high-density lipoprotein at 24, 48, and 96 weeks. Moreover, no significant difference was found between the two regimens (ATZ/r and DRV/r) in terms of change in visceral (SMD -0.06, 95%CI [-0.33, 0.21]) or subcutaneous adipose tissue (SMD 0.12, 95% CI [-0.15, 0.39]). The ATZ/r regimen was generally as effective and well-tolerated as the LPV/r regimen for the treatment of HIV-1 patients. Compared to the DRV/r regimen, ATZ/r has no favorable effect on the plasma lipid profile or adipose tissue distribution.
Topics: Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Atazanavir Sulfate; CD4 Lymphocyte Count; Darunavir; HIV Infections; HIV-1; Humans; Lopinavir; RNA, Viral; Randomized Controlled Trials as Topic; Ritonavir; Treatment Outcome; Viral Load
PubMed: 28361290
DOI: 10.1007/s00705-017-3346-9 -
PloS One 2015Some HIV antiretroviral therapies (ART) have been associated with renal toxicities, which become of increasing concern as HIV-infected patients age and develop... (Meta-Analysis)
Meta-Analysis Review
Some HIV antiretroviral therapies (ART) have been associated with renal toxicities, which become of increasing concern as HIV-infected patients age and develop comorbidities. The objective of this study was to evaluate the relative impact of atazanavir (ATV)-based regimens on the renal function of adult patients with HIV. We conducted a systematic literature review by searching PubMed, EMBASE, Cochrane library, and the CRD from 2000 until March 2013. Major HIV-related conferences occurring in the past two years were also searched. All randomized clinical trials and large cohort studies assessing renal function in treatment-naïve and/or treatment-experienced HIV patients on ATV-based regimens were included. Fixed-effect mixed-treatment network analyses were carried out on the most frequently reported renal outcomes. 23 studies met the inclusion criteria, and change in estimated glomerular filtration rate (eGFR) from baseline to 48 weeks was identified as the main outcome. Two networks including, respectively, six studies (using the Cockcroft-Gault method) and four studies (using MDRD and CKD-EPI) were analysed. With CG network, ATV/r + TDF/FTC was associated with lower impact on the decline of eGFR than ATV/cobicistat + TDF/FTC but with higher decrease in eGFR than ATV/r + ABC/3TC (difference in mean change from baseline in eGFR respectively +3.67 and -3.89). The use of ATV/cobicistat + TDF/FTC led to a similar decline in eGFR as EVG/cobicistat/TDF/FTC. With respect to third agents combined with TDF/FTC, ATV/r had a lower increase in eGFR in comparison to EFV, and no difference was shown when compared to SQV/r and DRV/r. The effect of ATV-based regimens on renal function at 48 weeks appears similar to other ART regimens and appears to be modest regardless of boosting agent or backbone, although TDF containing backbones consistently leads to greater decline in eGFR.
Topics: Adult; Anti-HIV Agents; Atazanavir Sulfate; Demography; Female; Glomerular Filtration Rate; HIV Infections; Humans; Kidney Function Tests; Male; Renal Insufficiency, Chronic; Risk Factors
PubMed: 25938588
DOI: 10.1371/journal.pone.0124666 -
Medicine Aug 2021Lopinavir, ritonavir, atazanavir, and saquinavir had been reportedly used or suggested for coronavirus disease 2019 (COVID-19) treatment. They may cause...
BACKGROUND
Lopinavir, ritonavir, atazanavir, and saquinavir had been reportedly used or suggested for coronavirus disease 2019 (COVID-19) treatment. They may cause electrocardiography changes. We aim to evaluate risk of PR prolongation, QRS widening, and QT prolongation from lopinavir, ritonavir, atazanavir, and saquinavir.
METHODS
In accordance with preferred reporting items for systematic reviews and meta-analyses guidelines, our search was conducted in PubMed Central, PubMed, EBSCOhost, and ProQuest from inception to June 25, 2020. Titles and abstracts were reviewed for relevance. Cochrane Risk of Bias Tool 2.0 and Downs and Black criteria was used to evaluate quality of studies.
RESULTS
We retrieved 9 articles. Most randomized controlled trials have low risk of biases while all quasi-experimental studies have a positive rating. Four studies reporting PR prolongation however only 2 studies with PR interval >200 ms. One of which, reported its association after treatment with ritonavir-boosted saquinavir treatment while another, during treatment with ritonavir-boosted atazanavir. No study reported QRS widening >120 ms with treatment. Four studies reporting QT prolongation, with only one study reaching QT interval >450 ms after ritonavir-boosted saquinavir treatment on healthy patients. There is only one study on COVID-19 patients reporting QT prolongation in 1 out of 95 patients after ritonavir-boosted lopinavir treatment.
CONCLUSION
Limited evidence suggests that lopinavir, ritonavir, atazanavir, and saquinavir could cause PR prolongation, QRS widening, and QT prolongation. Further trials with closer monitoring and assessment of electrocardiography are needed to ascertain usage safety of antivirals in COVID-19 era.
Topics: Adult; Atazanavir Sulfate; Cytochrome P-450 CYP3A Inhibitors; Drug Therapy, Combination; Electrocardiography; Humans; Long QT Syndrome; Lopinavir; Ritonavir; Saquinavir
PubMed: 34397829
DOI: 10.1097/MD.0000000000026787 -
African Health Sciences Mar 2020This systematic review and meta-analysis was conducted to evaluate the safety and effectiveness of Atazanavir/ritonavir over lopinavir/ritonavir in human... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This systematic review and meta-analysis was conducted to evaluate the safety and effectiveness of Atazanavir/ritonavir over lopinavir/ritonavir in human immunodeficiency virus-1 (HIV-1) infection.
METHODS
Clinical trials with a head-to-head comparison of atazanavir/ritonavir and lopinavir/ritonavir in HIV-1 were included. Electronic databases: PubMed/Medline CENTRAL, Embase, Scopus, and Web of Science were searched. Viral suppression below 50 copies/ml at the longest follow-up period was the primary outcome measure. Grade 2-4 treatment-related adverse drug events, lipid profile changes and grade 3-4 bilirubin elevations were used as secondary outcome measures.
RESULTS
A total of nine articles from seven trials with 1938 HIV-1 patients were included in the current study. Atazanavir/ritonavir has 13% lower overall risk of failure to suppress the virus level < 50 copies/ml than lopinavir/ritonavir in fixed effect model (pooled RR: 0.87; CI: 0.78, 0.96; P=0.006). The overall risk of hyperbilirubinemia is very high for atazanavir/ritonavir than lopinavir/ritonavir in the random effects model (pooled RR: 45.03; CI: 16.03, 126.47; P< 0.0001).
CONCLUSION
Atazanavir/ritonavir has a better viral suppression at lower risk of lipid abnormality than lopinavir/ritonavir. The risk and development of hyperbilirubinemia from atazanavir-based regimens should be taken into consideration both at the time of prescribing and patient follow-up.
Topics: Antiretroviral Therapy, Highly Active; Atazanavir Sulfate; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Hyperbilirubinemia; Lopinavir; Ritonavir; Treatment Outcome; Viral Load
PubMed: 33402897
DOI: 10.4314/ahs.v20i1.14 -
Antiviral Therapy 2014Despite increasing numbers of women with HIV worldwide, females are under-represented in clinical trials of antiretrovirals and literature addressing gender differences... (Review)
Review
BACKGROUND
Despite increasing numbers of women with HIV worldwide, females are under-represented in clinical trials of antiretrovirals and literature addressing gender differences in clinical outcomes, treatment discontinuation, adverse events and adherence are limited. Most recommendations specific to women in current guidelines relate to pregnant women or women wishing to become pregnant. The purpose of this systematic review is to provide clinicians with an overview of available literature regarding the use of ritonavir-boosted atazanavir (ATV/r) in women.
METHODS
The online databases PubMed and EMBASE, HIV-related conference abstracts and reference lists of relevant articles were searched according to predefined terms and limited to items published from 1 October 2007 to 1 October 2012. Updates to conference presentations were checked for substantive journal publication up to 28 November 2013.
RESULTS
Of the 294 initial citations retrieved, manual selection identified 19 relevant publications describing gender-based analyses of ATV/r. Publications describing gender-based differences in efficacy, safety, tolerability, pharmacokinetics, drug-drug interactions and adherence are critically evaluated.
CONCLUSIONS
As part of a combination antiretroviral therapy regimen, ATV/r appears to be a safe, effective and durable option for treatment-naive and early treatment-experienced patients with HIV-1 infection, including non-pregnant and pregnant women.
Topics: Adult; Anti-HIV Agents; Atazanavir Sulfate; Drug Administration Schedule; Drug Therapy, Combination; Female; HIV Infections; HIV-1; Humans; Male; Oligopeptides; Pregnancy; Pyridines; Ritonavir; Sex Factors; Treatment Outcome; Viral Load
PubMed: 24480797
DOI: 10.3851/IMP2742 -
The Annals of Pharmacotherapy Apr 2013To systematically examine the literature assessing the effect of uridine 5'-diphospho-glucuronosyltransferase (UGT)1A1*28 genetic polymorphisms on atazanavir-associated... (Review)
Review
OBJECTIVE
To systematically examine the literature assessing the effect of uridine 5'-diphospho-glucuronosyltransferase (UGT)1A1*28 genetic polymorphisms on atazanavir-associated hyperbilirubinemia.
DATA SOURCES
MEDLINE (1948-November 2012), EMBASE (1980-November 2012), International Pharmaceutical Abstracts (1970-November 2012), Google, and Google Scholar were searched using combinations of the following terms: glucuronosyltransferase, glucuronosyltransferase 1A1, atazanavir, atazanavir plus ritonavir, or polymorph$. The reference lists of all identified articles were manually searched.
STUDY SELECTION AND DATA EXTRACTION
Studies were included if at least 1 group of patients received atazanavir therapy and assessed the effect of UGT1A1*28 variants on bilirubin concentrations or atazanavir discontinuation rates. The quality of each study was ranked according to the US Preventive Services Task Force 1996 classification system. Information extracted included study design, baseline characteristics, treatment regimens, UGT1A1*28 genotype frequencies, bilirubin concentrations, incidence of hyperbilirubinemia, and atazanavir discontinuation rates.
DATA SYNTHESIS
Our search produced 12 studies, of which 9 were included (6 full manuscripts [level II-2], 2 abstracts, and 1 letter to the editor [level III]). Reported UGT1A1*28 homozygote genotype frequencies (0.8-23.8%) were in general agreement with the literature for the diverse ethnic population captured in the 9 studies. An association between the incidence of hyperbilirubinemia and UGT1A1*28 genotype (homozygotes > heterozygotes > wild-type) was demonstrated in all studies that reported such data (6 of 9 studies). However, the calculated positive predictive value for homozygosity and hyperbilirubinemia from pooled data was low (40.3%). Only 2 studies (levels II-2 and III) reported rates of atazanavir discontinuation due to hyperbilirubinemia and showed some positive correlation with presence of the UGT1A1*28 allele.
CONCLUSIONS
Based on the available evidence, homozygosity of the UGT1A1*28 allele does not strongly predict the incidence of severe hyperbilirubinemia. Thus, until large, prospective trials demonstrate otherwise, UGT1A1*28 testing does not appear to provide additional information to aid clinical decision-making when initiating atazanavir treatment in HIV-infected patients.
Topics: Alleles; Anti-HIV Agents; Atazanavir Sulfate; Glucuronosyltransferase; HIV Infections; Homozygote; Humans; Hyperbilirubinemia; Oligopeptides; Polymorphism, Genetic; Prospective Studies; Pyridines; Retrospective Studies
PubMed: 23548653
DOI: 10.1345/aph.1R550 -
HIV Medicine May 2014Treatment simplification involving induction with a ritonavir (RTV)-boosted protease inhibitor (PI) replaced by a nonboosted PI (i.e. atazanavir) has been shown to be a... (Meta-Analysis)
Meta-Analysis Review
A meta-analysis of the efficacy and safety of unboosted atazanavir compared with ritonavir-boosted protease inhibitor maintenance therapy in HIV-infected adults with established virological suppression after induction.
OBJECTIVES
Treatment simplification involving induction with a ritonavir (RTV)-boosted protease inhibitor (PI) replaced by a nonboosted PI (i.e. atazanavir) has been shown to be a viable option for long-term antiretroviral therapy. To evaluate the clinical evidence for this approach, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating efficacy and safety in patients with established virological suppression.
METHODS
Several databases were searched without limits on time or language. Searches of conferences were also conducted. RCTs were included if they compared a PI/RTV regimen to unboosted atazanavir, after induction with PI/RTV. The meta-analysis was conducted using a random effects model for the proportion achieving virological suppression (i.e. HIV RNA < 50 and <400 HIV-1 RNA copies/mL), CD4 cell counts, lipid levels and liver function tests. Dichotomous outcomes were reported as risk ratios (RRs) and continuous outcomes as mean differences (MDs).
RESULTS
Five studies (n = 1249) met the inclusion criteria. The meta-analysis demonstrated no statistically significant difference in efficacy (i.e. HIV RNA < 50 copies/mL) between PI/RTV and unboosted atazanavir [RR = 1.04; 95% confidence interval (CI) 0.99 to 1.10], with no heterogeneity. Findings were similar in a subanalysis of studies where atazanavir/RTV was the only PI/RTV used during induction. Additional efficacy results support these findings. A significant reduction in total cholesterol (P < 0.00001), triglycerides (P = 0.0002), low-density lipoprotein (LDL) cholesterol (P = 0.009) and hyperbilirubinaemia (P = 0.02) was observed with unboosted atazanavir vs. PI/RTV.
CONCLUSIONS
The meta-analysis demonstrated that switching patients with virological suppression from an RTV-boosted PI to unboosted atazanavir leads to improvements in safety (i.e. blood parameter abnormalities) without sacrificing virological efficacy.
Topics: Atazanavir Sulfate; Drug Substitution; Drug Therapy, Combination; HIV Infections; Humans; Maintenance Chemotherapy; Oligopeptides; Protease Inhibitors; Pyridines; Randomized Controlled Trials as Topic; Ritonavir
PubMed: 24314017
DOI: 10.1111/hiv.12118 -
A combination drug of abacavir-lamivudine-zidovudine (Trizivir) for treating HIV infection and AIDS.The Cochrane Database of Systematic... Jul 2009The human immunodeficiency virus (HIV) has become one of the greatest challenges to global public health. In 2007 UNAIDS estimated that 33.2 million people were living... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The human immunodeficiency virus (HIV) has become one of the greatest challenges to global public health. In 2007 UNAIDS estimated that 33.2 million people were living with HIV. Currently recommended regimens for initiating HIV treatment consist of either a non-nucleoside reverse transcriptase inhibitor (NNRTI) or ritonvair-boosted protease inhibitor (PI) combined with two nucleoside reverse transcriptase inhibitors (NRTIs); however, there may be some patients for whom NNRTIs and PIs may not be appropriate.
OBJECTIVES
The aim of this review was to evaluate the effects of Trizivir, a fixed-dose combination of three NRTIs (abacavir-lamivudine-zidovudine) for initial treatment of HIV infection.
SEARCH STRATEGY
In February 2008, we searched the Cochrane Library, PubMed, EMBASE, AIDSearch and GATEWAY and checked reference lists of identified articles. In May 2009, we repeated the search in PubMed and the Cochrane Library.
SELECTION CRITERIA
We selected randomized controlled trials (RCTs) with a minimum follow-up time of six months which compared Trizivir with either a PI- or NNRTI-based therapy among antiretroviral-naive HIV-infected patients aged at least 13 years.
DATA COLLECTION AND ANALYSIS
Three authors independently extracted data. We calculated the relative risk (RR) or mean difference (as appropriate) for each outcome with its 95% confidence interval (CI) and conducted meta-analysis using the random-effects method because of significant statistical heterogeneity (P<0.1).
MAIN RESULTS
We identified nine potentially eligible RCTs, three of which met our inclusion criteria. One trial compared Trizivir to efavirenz (an NNRTI) plus two or three NRTIs; the second trial compared Trizivir to a treatment based on the PI nelfinavir; and the third compared Trizivir to atazanavir (a PI) plus two NRTIs. Overall, there was no significant difference in the incidence of virological failure between participants on Trizivir and those on PI-based or NNRTI-based therapy (three trials, N=1687; RR 1.14, 95% CI 0.56 to 2.32). However, there was significant heterogeneity between the results of the three trials (heterogeneity P=0.009, I(2)=79%), with a significant increase in virological failure for Trizivir compared to efavirenz (N=1147; RR 1.93, 95% CI 1.46 to 2.55) but no difference between Trizivir and PIs (two trials, N=540; RR 0.82, 95% CI 0.50 to 1.36). We found no significant differences between Trizivir and either the PI or NNRTI on CD4+ cell counts (standardized mean difference -0.01, 95% CI -0.11 to 0.09, heterogeneity P=0.59, I(2)=0%), severe adverse events (RR 1.41, 95% CI 0.61 to 3.25, heterogeneity P=0.03, I(2)=73%) and hypersensitivity reactions (RR 4.04, 95% CI 0.41 to 40.02, heterogeneity P=0.03, I(2)=72%). Only the studies involving PIs reported the effect of the treatment regimens on the lipid profile. One study found that at 96 weeks, the mean increase in total cholesterol from baseline was significantly lower with Trizivir than with nelfinavir, but there were no significant differences with triglyceride levels. The second study found the fasting lipid profile to be comparable in both the Trizivir and atazanavir arms at 48 weeks.
AUTHORS' CONCLUSIONS
Our findings indicate that Trizivir remains a viable option for initiating antiretroviral therapy, especially in HIV-infected patients with pre-existing hyperlipidaemia and those who do not tolerate ritonavir.
Topics: Acquired Immunodeficiency Syndrome; Alkynes; Anti-HIV Agents; Atazanavir Sulfate; Benzoxazines; Cyclopropanes; Drug Combinations; HIV Infections; Humans; Lamivudine; Nelfinavir; Oligopeptides; Pyridines; Randomized Controlled Trials as Topic; Zidovudine
PubMed: 19588374
DOI: 10.1002/14651858.CD005481.pub2 -
The Cochrane Database of Systematic... Mar 2013UNAIDS estimates that 34 million people are currently living with the human immunodeficiency virus (HIV) worldwide. Currently recommended regimens for initiating HIV... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
UNAIDS estimates that 34 million people are currently living with the human immunodeficiency virus (HIV) worldwide. Currently recommended regimens for initiating HIV treatment consist of either a non-nucleoside reverse transcriptase inhibitor (NNRTI) or ritonavir-boosted protease inhibitor (PI) combined with two nucleoside reverse transcriptase inhibitors (NRTIs). However, there may be some patients for whom NNRTIs and PIs may not be appropriate. This is an update of the review published in the Cochrane Library Issue 3, 2009.
OBJECTIVES
To evaluate the effects of any fixed-dose combination of three NRTIs (co-formulated abacavir-lamivudine-zidovudine) for initial treatment of HIV infection.
SEARCH METHODS
Between December 2010 and July 2011, we used standard Cochrane methods to search electronic databases and conference proceedings with relevant search terms without limits to language or publication status.
SELECTION CRITERIA
We selected randomised controlled trials (RCTs) with a minimum follow-up time of six months which compared co-formulated abacavir-lamivudine-zidovudine with either PI-based or NNRTI-based therapy among antiretroviral-naive HIV-infected patients aged at least 13 years.
DATA COLLECTION AND ANALYSIS
Three authors independently selected eligible studies, assessed risk of bias, and extracted data; resolving discrepancies by consensus. We calculated the risk ratio (RR) or mean difference (MD), as appropriate, with its 95% confidence interval (CI) and conducted meta-analysis using the random-effects method because of significant statistical heterogeneity (P<0.1).
MAIN RESULTS
We identified 15 potentially eligible RCTs, four of which met our inclusion criteria. The four included RCTs were conducted in the United States of America (USA); USA, Puerto Rico, Guatemala, Dominican Republic, and Panama; USA and Mexico; and Botswana, respectively. The RCTs compared co-formulated abacavir-lamivudine-zidovudine to treatment based on efavirenz (NNRTI), nelfinavir (PI), atazanavir (PI), and co-formulated lopinavir-ritonavir (PI), respectively. Overall, there was no significant difference in virological suppression between co-formulated abacavir-lamivudine-zidovudine and NNRTI- or PI-based therapy (4 trials; 2247 participants: RR 0.73, 95% CI 0.39 to 1.36). However, the results showed significant heterogeneity (I(2)=79%); with co-formulated abacavir-lamivudine-zidovudine inferior to NNRTI (1 trial, 1147 participants: RR 0.35, 95%CI 0.26 to 0.49) but with a trend towards co-formulated abacavir-lamivudine-zidovudine being superior to PI (3 trials, 1110 participants: RR 1.07, 95%CI 1.00 to 1.16; I(2)=0%). We found no significant differences between co-formulated abacavir-lamivudine-zidovudine and either PI or NNRTI on CD4+ cell counts (3 trials, 1687 participants: MD -0.01, 95%CI -0.11 to 0.09; I(2)=0%), severe adverse events (4 trials: RR 1.22, 95%CI 0.78 to 1.92; I(2)=62%) and hypersensitivity reactions (4 trials: RR 4.04, 95% CI 0.41 to 40.02; I(2)=72%). Only two studies involving PIs reported data on the lipid profile. One study found that the mean increase in total cholesterol from baseline to 96 weeks was significantly lower with co-formulated abacavir-lamivudine-zidovudine than with nelfinavir, but there were no differences with triglyceride levels. The second study found the fasting lipid profile to be comparable in both co-formulated abacavir-lamivudine-zidovudine and atazanavir arms at 48 weeks.The significant heterogeneity of effects for most outcomes evaluated was largely due to differences in the control therapy used in the included trials (i.e. NNRTIs or PIs). Using the GRADE approach, we rated the overall quality of the evidence on the relative effects of co-formulated abacavir-lamivudine-zidovudine for initial treatment of HIV infection as moderate. The main reason for downgrading the quality of the evidence was imprecision of the findings. The estimate of the treatment effect for each outcome has wide confidence intervals, which extend from the fixed-dose NRTI combination regimen being appreciably better to the regimen being appreciably worse than PI- or NNRTI-based regimens.
AUTHORS' CONCLUSIONS
This review provides evidence that co-formulated abacavir-lamivudine-zidovudine remains a viable option for initiating antiretroviral therapy, especially in HIV-infected patients with pre-existing hyperlipidaemia. The varied geographical locations of the included trials augment the external validity of these findings. We are moderately confident in our estimate of the treatment effects of the triple NRTI regimen as initial therapy for HIV infection. In the context of the GRADE approach, such moderate quality of evidence implies that the true effects of the regimen are likely to be close to the estimate of effects found in this review; but there is a possibility that they could be substantially different. Further research should be geared towards defining the subgroup of HIV patients for whom this regimen will be most beneficial.
Topics: Acquired Immunodeficiency Syndrome; Alkynes; Anti-HIV Agents; Atazanavir Sulfate; Benzoxazines; Cyclopropanes; Dideoxynucleosides; Drug Combinations; HIV Infections; Humans; Lamivudine; Nelfinavir; Oligopeptides; Pyridines; Randomized Controlled Trials as Topic; Zidovudine
PubMed: 23543540
DOI: 10.1002/14651858.CD005481.pub3