Clinical Profile of Cyclooxygenase-2 Inhibitors in Treating Non-Small Cell Lung Cancer: A Meta-Analysis of Nine Randomized Clinical Trials

Background

Evidence on the benefits of combining cyclooxygenase-2 inhibitor (COX-2) in treating non-small cell lung cancer (NSCLC) is still controversial. We investigated the efficacy and safety profile of cyclooxygenase-2 inhibitors in treating NSCLC.

Methods

The first meta-analysis of eligible studies was performed to assess the effect of COX-2 inhibitors for patients with NSCLC on the overall response rate (ORR), overall survival (OS), progression-free survival (PFS), one-year survival, and toxicities. The fixed-effects model was used to calculate the pooled RR and HR and between-study heterogeneity was assessed. Subgroup analyses were conducted according to the type of COX-2 inhibitors, treatment pattern, and treatment line.

Results

Nine randomized clinical trials, comprising 1679 patents with NSCLC, were included in the final meta-analysis. The pooled ORR of patients who have NSCLC with COX-2 inhibitors was significantly higher than that without COX-2 inhibitors. In subgroup analysis, significantly increased ORR results were found on celecoxib (RR = 1.29, 95% CI: 1.09, 1.51), rofecoxib (RR = 1.61, 95% CI: 1.14, 2.28), chemotherapy (RR = 1.40, 95% CI: 1.20, 1.63), and first-line treatment (RR = 1.39, 95% CI: 1.19, 1.63). However, COX-2 inhibitors had no effect on the one-year survival, OS, and PFS. Increased RR of leucopenia (RR = 1.21, 95% CI: 1.01, 1.45) and thrombocytopenia (RR = 1.36, 95% CI: 1.06, 1.76) suggested that COX-2 inhibitors increased hematologic toxicities (grade ≥ 3) of chemotherapy

Conclusions

COX-2 inhibitors increased ORR of advanced NSCLC and had no impact on survival indices, but it may increase the risk of hematologic toxicities associated with chemotherapy.     

Comparison of Operative and Non-Operative Treatment of Acute Undisplaced or Minimally-Displaced Scaphoid Fractures: A Meta-Analysis of Randomized Controlled Trials

Background

Traditionally, acute undisplaced or minimally-displaced scaphoid fractures are treated by casting in short- or long-arm casts. Although reports have shown that operative treatment is safe, effective and produces satisfactory results, outcomes from current studies comparing these two methods are questionable. The aim of this meta-analysis was to evaluate the effects of operative versus non-operative treatment for acute undisplaced or minimally-displaced scaphoid fractures in adults.

Methods

Computerized searches were performed without language restrictions and all randomized controlled studies providing information on the effects of operative versus non-operative treatment on the outcomes of acute undisplaced or minimally-displaced scaphoid fractures were included. The weighted and standard mean difference (WMD and SMD) or the relative risk (RR) were calculated for continuous or dichotomous data respectively.

Results

A total of six studies reported in seven publications were included, representing data on 340 fractures. Meta-analysis indicated that operative treatment resulted in significantly better functional outcomes in the short term when compared with non-operative treatment. Consistently, patients who accepted surgery had a more rapid return to work. Further, surgery was advantageous in preventing delayed union of the fractures, a finding supported by the results of analysis of the time to fracture union. A number-needed-to-treat analysis revealed that more than 20 patients would have to undergo operative treatment to prevent one delayed union.

Conclusion

Acute undisplaced or minimally-displaced scaphoid fractures demonstrate faster recovery with operative treatment; however, the current meta-analysis does not provide evidence supporting the routine use of operative treatment for all acute undisplaced or minimally-displaced scaphoid fractures.     

Intentional Weight Loss and All-Cause Mortality: A Meta-Analysis of Randomized Clinical Trials

Background

Obesity is associated with increased mortality, and weight loss trials show rapid improvement in many mortality risk factors. Yet, observational studies typically associate weight loss with higher mortality risk. The purpose of this meta-analysis of randomized controlled trials (RCTs) of weight loss was to clarify the effects of intentional weight loss on mortality.

Methods

2,484 abstracts were identified and reviewed in PUBMED, yielding 15 RCTs reporting (1) randomization to weight loss or non-weight loss arms, (2) duration of ≥18 months, and (3) deaths by intervention arm. Weight loss interventions were all lifestyle-based. Relative risks (RR) and 95% confidence intervals (95% CI) were estimated for each trial. For trials reporting at least one death (n = 12), a summary estimate was calculated using the Mantel-Haenszel method. Sensitivity analysis using sparse data methods included remaining trials.

Results

Trials enrolled 17,186 participants (53% female, mean age at randomization = 52 years). Mean body mass indices ranged from 30–46 kg/m², follow-up times ranged from 18 months to 12.6 years (mean: 27 months), and average weight loss in reported trials was 5.5±4.0 kg. A total of 264 deaths were reported in weight loss groups and 310 in non-weight loss groups. The weight loss groups experienced a 15% lower all-cause mortality risk (RR = 0.85; 95% CI: 0.73–1.00). There was no evidence for heterogeneity of effect (Cochran’s Q = 5.59 (11 d.f.; p = 0.90); I² = 0). Results were similar in trials with a mean age at randomization ≥55 years (RR = 0.84; 95% CI 0.71–0.99) and a follow-up time of ≥4 years (RR = 0.85; 95% CI 0.72–1.00).

Conclusions

In obese adults, intentional weight loss may be associated with approximately a 15% reduction in all-cause mortality.     

Shensongyangxin Capsules for Paroxysmal Atrial Fibrillation: A Systematic Review of Randomized Clinical Trials

Objective

To evaluate the evidence for the effectiveness and safety of Shensongyangxin Capsules (SSYX) for treating paroxysmal atrial fibrillation (PAF).

Methods

We searched for randomized clinical trials for SSYX in PAF up to June 2015. The Cochrane risk of bias tool was used to assess the methodological quality. RevMan 5.3 was used to synthesize the results.

Results

We included 22 trials involving 2,347 PAF patients. The quality of the included studies was generally poor. The results of the meta-analysis showed that SSYX plus routine treatment was more effective at improving P-wave dispersion (Pwd) and the frequency of PAF attacks compared with routine treatment alone. The results from the included trials that compared SSYX plus routine treatment and arrhythmic drugs plus routine treatment were inconsistent. Trials reported on Pwd, quality of life, frequency of PAF attacks or maintenance rate of sinus rhythm and found that SSYX combined with anti-arrhythmic drugs plus routine treatment was more effective than anti-arrhythmic drugs plus routine treatment. Four of the trials reported adverse events, indicating that SSYX was potentially safer than anti-arrhythmic drugs.

Conclusions

There appears to be some benefit from the use of SSYX. However, due to poor methodological quality, we could not draw confirmative conclusions regarding the beneficial effect of using SSYX.     

Post-Operative Auto-Transfusion in Total Hip or Knee Arthroplasty: A Meta-Analysis of Randomized Controlled Trials

Background

Total hip or knee arthroplasty is an elective procedure that is usually accompanied by substantial blood loss, which may lead to acute anemia. As a result, almost half of total joint arthroplasty patients receive allogeneic blood transfusions (ABT). Many studies have shown that post-operative auto-transfusion (PAT) significantly reduces the need for ABT, but other studies have questioned the efficacy of this method.

Methods

The protocol for this trial and supporting CONSORT checklist are available as supporting information; see Checklist S1. To evaluate the efficacy of PAT, we conducted a Cochrane systematic review that combined all available data from randomized controlled trials. Data from the six included trials were pooled for analysis. We then calculated relative risks with 95% confidence intervals (CIs) for dichotomous outcomes and mean differences with 95% CIs for continuous outcomes.

Findings and Conclusion

To our knowledge, this is the first meta-analysis to compare the clinical results between PAT and a control in joint replacement patients. This meta-analysis has proven that the use of a PAT reinfusion system reduced significantly the demand for ABT, the number of patients who require ABT and the cost of hospitalization after total knee and hip arthroplasty. This study, together with other previously published data, suggests that PAT drains are beneficial. Larger, sufficiently powered studies are necessary to evaluate the presumed reduction in the incidence of infection as well as DVT after joint arthroplasty with the use of PAT.     

Evidence for the Selective Reporting of Analyses and Discrepancies in Clinical Trials: A Systematic Review of Cohort Studies of Clinical Trials

Background

Most publications about selective reporting in clinical trials have focussed on outcomes. However, selective reporting of analyses for a given outcome may also affect the validity of findings. If analyses are selected on the basis of the results, reporting bias may occur. The aims of this study were to review and summarise the evidence from empirical cohort studies that assessed discrepant or selective reporting of analyses in randomised controlled trials (RCTs).

Methods and Findings

A systematic review was conducted and included cohort studies that assessed any aspect of the reporting of analyses of RCTs by comparing different trial documents, e.g., protocol compared to trial report, or different sections within a trial publication. The Cochrane Methodology Register, Medline (Ovid), PsycInfo (Ovid), and PubMed were searched on 5 February 2014. Two authors independently selected studies, performed data extraction, and assessed the methodological quality of the eligible studies. Twenty-two studies (containing 3,140 RCTs) published between 2000 and 2013 were included. Twenty-two studies reported on discrepancies between information given in different sources. Discrepancies were found in statistical analyses (eight studies), composite outcomes (one study), the handling of missing data (three studies), unadjusted versus adjusted analyses (three studies), handling of continuous data (three studies), and subgroup analyses (12 studies). Discrepancy rates varied, ranging from 7% (3/42) to 88% (7/8) in statistical analyses, 46% (36/79) to 82% (23/28) in adjusted versus unadjusted analyses, and 61% (11/18) to 100% (25/25) in subgroup analyses. This review is limited in that none of the included studies investigated the evidence for bias resulting from selective reporting of analyses. It was not possible to combine studies to provide overall summary estimates, and so the results of studies are discussed narratively.

Conclusions

Discrepancies in analyses between publications and other study documentation were common, but reasons for these discrepancies were not discussed in the trial reports. To ensure transparency, protocols and statistical analysis plans need to be published, and investigators should adhere to these or explain discrepancies. Please see later in the article for the Editors'' Summary     

Comparison of Clinical Efficacy and Safety between Indacaterol and Tiotropium in COPD: Meta-Analysis of Randomized Controlled Trials

Two once-daily inhaled bronchodilators, indacaterol and tiotropium, are widely used as first-line therapy in stable COPD patients. This study was performed to compare the clinical efficacy and safety between indacaterol and tiotropium in patients with moderate-to-severe COPD. MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials were searched to identify all published randomized controlled trials (RCTs). The primary outcome was trough forced expiratory volume in 1 second (FEV₁) at week 12. Four RCTs were eligible for inclusion (three RCTs with moderate-to-severe COPD patients and one RCT with only severe COPD patients). Trough FEV₁ at weeks 12 and 26 were not significantly different between indacaterol and tiotropium by the standardized mean difference with 0.014 (95% CI, -0.036, 0.063, I²= 23.5%) and with 0.037 (95% CI, -0.059 to 0.133, I²= 0%) along with differences in means of 0.003L and 0.014L, respectively. Indacaterol and tiotropium also showed similar St. George`s Respiratory Questionnaire (SGRQ) total scores and percentages of patients with SGRQ improvement (≥ 4 units) at week 26. The incidences of nasopharyngitis, serious cardiovascular events, and serious adverse events were not different between indacaterol and tiotropium, while those of cough (OR = 1.68, P < 0.001, and RR = 1.63) and COPD worsening (OR = 1.18, P = 0.003, and RR = 1.12) were higher for indacaterol than tiotropium. However, when one study with only severe COPD patients was removed from the meta-analysis, the difference in the incidence of COPD worsening between indacaterol and tiotropium became non-significant (OR = 1.13, P = 0.204, and RR = 1.09). The clinical efficacy and serious adverse events between indacaterol and tiotropium were equivocal in patients with moderate-to-severe COPD. Cough is a common complaint associated with indacaterol, and COPD worsening needs to be carefully monitored in severe COPD patients when treated with indacaterol.     

Effectiveness of Pulsed Electromagnetic Fields on Bone Healing: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

The effect of pulsed electromagnetic field (PEMF) on bone healing is still uncertain and it has not been established as a standardized treatment. The aim of this systematic review and meta-analysis is to evaluate the effect of PEMF on bone healing in patients with fracture. We searched CNKI, Wan Fang, VIP, EMbase, PubMed, CENTRAL, Web of Science, Physiotherapy Evidence Database, and Open Grey websites for randomized controlled trials (published before July 2019 in English or Chinese) comparing any form of PEMF to sham. Reference lists were also searched. Related data were extracted by two investigators independently. The bias risk of the articles and the evidence strength of the outcomes were evaluated. Twenty-two studies were eligible and included in our analysis (n = 1,468 participants). The pooled results of 14 studies (n = 1,131 participants) demonstrated that healing rate in PEMF group was 79.7% (443/556), and that in the control group was 64.3% (370/575). PEMF increased healing rate (RR = 1.22; 95% confidence interval [CI] = 1.10–1.35; I² = 48%) by the Mantel–Haenszel analysis, relieved pain (standardized mean difference (SMD) = −0.49; 95% CI = −0.88 to −0.10; I² = 60%) by the inverse variance analysis, and accelerated healing time (SMD = −1.01; 95% CI = −2.01 to −0.00; I² = 90%) by the inverse variance analysis. Moderate quality evidence suggested that PEMF increased healing rate and relieved pain of fracture, and very low-quality evidence showed that PEMF accelerated healing time. Larger and higher quality randomized controlled trials and pre-clinical studies of optimal frequency, amplitude, and duration parameters are needed. © 2020 Bioelectromagnetics Society.     

Randomized Controlled Trials of Maternal‐Fetal Surgery: A Challenge to Clinical Equipoise

This article focuses on maternal‐fetal surgery (MFS) and on the concept of clinical equipoise that is a widely accepted requirement for conducting randomized controlled trials (RCT). There are at least three reasons why equipoise is unsuitable for MFS. First, the concept is based on a misconception about the nature of clinical research and the status of research subjects. Second, given that it is not clear who the research subject/s in MFS is/are, if clinical equipoise is to be used as a criterion to test the ethical appropriateness of RCT, its meaning should be unambiguous. Third, because of the multidisciplinary character of MFS, it is not clear who should be in equipoise. As a result, we lack an adequate criterion for the ethical review of MFS protocols. In our account, which is based on Chervenak and McCullough's seminal work in the field of obstetric ethics, equipoise is abandoned. and RCT involving MFS can be ethically initiated when a multidisciplinary ethics review board (ERB), having an evidence‐based assessment of the risks involved, is convinced that the value of answering the research hypothesis, for the sake of the health interests of future pregnant women carrying fetuses with certain congenital birth defects, justifies the actual risks research participants might suffer within a set limit of low/manageable.     

Using Ecological Momentary Assessment in Testing the Effectiveness of an Alcohol Intervention: A Two-Arm Parallel Group Randomized Controlled Trial

Background

Alcohol consumption of college students has a fluctuating nature, which might impact the measurement of intervention effects. By using 25 follow-up time-points, this study tested whether intervention effects are robust or might vary over time.

Methods

Data were used from a two-arm parallel group randomized controlled trial applying ecological momentary assessment (EMA) with 30 data time-points in total. Students between 18 and 24 years old who reported heavy drinking in the past six months and who were ready to change their alcohol consumption were randomly assigned to the experimental (n = 456: web-based brief alcohol intervention) and control condition (n = 451: no intervention). Outcome measures were weekly alcohol consumption, frequency of binge drinking, and heavy drinking status.

Results

According to the intention-to-treat principle, regression analyses revealed that intervention effects on alcohol consumption varied when exploring multiple follow-up time-points. Intervention effects were found for a) weekly alcohol consumption at 1, 2, 3, 4, and 7 weeks follow-up, b) frequency of binge drinking at 1, 2, 7, and 12 weeks follow-up, and c) heavy drinking status at 1, 2, 7, and 16 weeks follow-up.

Conclusions

This research showed that the commonly used one and six month follow-up time-points are relatively arbitrary and not using EMA might bring forth erroneous conclusions on the effectiveness of interventions. Therefore, future trials in alcohol prevention research and beyond are encouraged to apply EMA when assessing outcome measures and intervention effectiveness.

Trial registration

Netherlands Trial Register NTR2665     

Efficacy of Intensive Control of Glucose in Stroke Prevention: A Meta-Analysis of Data from 59197 Participants in 9 Randomized Controlled Trials

Background

The efficacy of treatments that lower glucose in reducing the risk of incident stroke remains unclear. We therefore did a systematic review and meta-analysis to evaluate the efficacy of intensive control of glucose in the prevention of stroke.

Methodology/Principal Findings

We systematically searched Medline, EmBase, and the Cochrane Library for trials published between 1950 and June, 2012. We included randomized controlled trials that reported on the effects of intensive control of glucose on incident stroke compared with standard care. Summary estimates of relative risk (RR) reductions were calculated with a random effects model, and the analysis was further stratified by factors that could affect the treatment effects. Of 649 identified studies, we included nine relevant trials, which provided data for 59197 patients and 2037 events of stroke. Overall, intensive control of glucose as compared to standard care had no effect on incident stroke (RR, 0.96; 95%CI 0.88–1.06; P = 0.445). In the stratified analyses, a beneficial effect was seen in those trials when body mass index (BMI) more than 30 (RR, 0.86; 95%CI: 0.75–0.99; P = 0.041). No other significant differences were detected between the effect of intensive control of glucose and standard care when based on other subset factors.

Conclusions/Significance

Our study indicated intensive control of glucose can effectively reduce the risk of incident stroke when patients with BMI more than 30.     

Compliance with Once-Daily versus Twice or Thrice-Daily Administration of Antibiotic Regimens: A Meta-Analysis of Randomized Controlled Trials

Objective

To investigate whether compliance of patients to antibiotic treatment is better when antibiotics are administered once than multiple times daily.

Methods

We performed a systematic search in PubMed and Scopus databases. Only randomized controlled trials were considered eligible for inclusion. Compliance to antibiotic treatment was the outcome of the meta-analysis.

Results

Twenty-six studies including 8246 patients with upper respiratory tract infections in the vast majority met the inclusion criteria. In total, higher compliance was found among patients treated with once-daily treatment than those receiving treatment twice, thrice or four times daily [5011 patients, RR=1.22 (95% CI, 1.11, 1.34]. Adults receiving an antibiotic once-daily were more compliant than those receiving the same antibiotic multiple times daily [380 patients, RR=1.09 (95% CI, 1.02, 1.16)]. Likewise, children that received an antibiotic twice-daily were more compliant than those receiving the same antibiotic thrice-daily [2118 patients, RR=1.10 (95% CI, 1.02, 1.19)]. Higher compliance was also found among patients receiving an antibiotic once compared to those receiving an antibiotic of different class thrice or four times daily [395 patients, RR=1.20 (95% CI, 1.12, 1.28)]. The finding of better compliance with lower frequency daily was consistent regardless of the study design, and treatment duration.

Conclusion

This meta-analysis showed that compliance to antibiotic treatment might be associated with higher when an antibiotic is administered once than multiple times daily for the treatment of specific infections and for specific classes of antibiotics.     

Vitamin D Supplementation and Breast Cancer Prevention: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

In recent years, the scientific evidence linking vitamin D status or supplementation to breast cancer has grown notably. To investigate the role of vitamin D supplementation on breast cancer incidence, we conducted a systematic review and meta-analysis of randomized controlled trials comparing vitamin D with placebo or no treatment. We used OVID to search MEDLINE (R), EMBASE and CENTRAL until April 2012. We screened the reference lists of included studies and used the “Related Article” feature in PubMed to identify additional articles. No language restrictions were applied. Two reviewers independently extracted data on methodological quality, participants, intervention, comparison and outcomes. Risk Ratios and 95% Confident Intervals for breast cancer were pooled using a random-effects model. Heterogeneity was assessed using the I² test. In sensitivity analysis, we assessed the impact of vitamin D dosage and mode of administration on treatment effects. Only two randomized controlled trials fulfilled the pre-set inclusion criteria. The pooled analysis included 5372 postmenopausal women. Overall, Risk Ratios and 95% Confident Intervals were 1.11 and 0.74–1.68. We found no evidence of heterogeneity. Neither vitamin D dosage nor mode of administration significantly affected breast cancer risk. However, treatment efficacy was somewhat greater when vitamin D was administered at the highest dosage and in combination with calcium (Risk Ratio 0.58, 95% Confident Interval 0.23–1.47 and Risk Ratio 0.93, 95% Confident Interval 0.54–1.60, respectively). In conclusions, vitamin D use seems not to be associated with a reduced risk of breast cancer development in postmenopausal women. However, the available evidence is still limited and inadequate to draw firm conclusions. Study protocol code: FARM8L2B5L.     

Teicoplanin as an Effective Alternative to Vancomycin for Treatment of MRSA Infection in Chinese Population: A Meta-analysis of Randomized Controlled Trials

Objective

To evaluate whether teicoplanin could be an alternative to vancomycin for treatment of MRSA infection in Chinese population using a meta-analysis in randomized controlled trials.

Methods

The following databases were searched: Chinese Biomedical Literature database (CBM), Chinese Journal Full-text database (CNKI), Wanfang database, Medline database, Ovid database and Cochrane Library. Articles published from 2002 to 2013 that studied teicoplanin in comparison to vancomycin in the treatment of MRSA infected patients were collected. Overall effects, publishing bias analysis and sensitivity analysis on clinical cure rate, microbiologic eradication rate and adverse events rate were performed by using Review Manager 5.2 and Stata 11.0 softwares.

Results

Twelve articles met entry criteria. There was no statistically significant difference between the two groups regarding the clinical cure rate (risk ratio [RR], teicoplanin vs vancomycin, 0.94; 95% CI, 0.74∼1.19; P = 0.60), microbiological cure rate (risk ratio [RR], teicoplanin vs vancomycin, 0.99; 95% CI, 0.91∼1.07; P = 0.74) and adverse event rate (risk ratio [RR], teicoplanin vs vancomycin, 0.86; 95% CI, 0.40∼1.84; P = 0.70).

Conclusions

The meta-analysis results indicate that the two therapies are similar in both efficacy and safety, thus teicoplanin can act as an effective alternative to vancomycin for treating patients infected by MRSA.     

Idraparinux or Idrabiotaparinux for Long-Term Venous Thromboembolism Treatment: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background

Venous thromboembolism (VTE) is a prevalent disease with potential serious consequences. Idraparinux and idrabiotaparinux are two kinds of long-acting pentasaccharides. Evidence has shown that idraparinux and idrabiotaparinux are effective anticoagulants. However, up to now, there is no consensus on whether they are better than other anticoagulation methods for long-term VTE treatment.

Objective

To evaluate the effect of idraparinux or idrabiotaparinux versus other anticoagulation methods for long-term VTE treatment.

Methods

We searched Cochrane Central Register of Controlled Trials, PubMed, Embase, Web of science, clinical trial registry web sites (clinical trials,WHO clinical trial registry), Googlescholar, PubMed related articles and companies'' web sites electronically up to Dec 30^th, 2012 and manually searched the reference lists and conference proceedings. Only randomized controlled trial (RCT) involving adult patients comparing idraparinux and/or idrabiotaparinux versus other anticoagulation methods for long-term VTE treatment was included. Two reviewers evaluated the studies and extracted data independently. Pooled risk ratios (RRs) were calculated as outcome measures and Revman 5.2 software was used to analyze data. Our primary efficacy and safety outcomes were the recurrent VTE and major bleeding rates.

Results

We included four RCTs and involved 8584 participants on idraparinux or idrabiotaparinux versus standard warfarin for VTE treatment from 9364 references. We did not perform meta-analysis on the VTE rate because of the significant heterogeneity. We used the fixed effect model to analyze the safety outcomes and demonstrated that idraparinux or idrabiotaparinux decreased major bleeding rate significantly (RR 0.73, 95% CI 0.54 to 0.98, P = 0.04) but had a trend to increase the all cause mortality (RR 1.26, 95% CI 1.00 to 1.57, P = 0.05) compared with warfarin.

Conclusions

Until now there is not sufficient evidence to clarify whether idraparinux or idrabiotaparinux is as effective and safe as the standard warfarin treatment for VTE treatment.     

Virologic Response to Tipranavir-Ritonavir or Darunavir-Ritonavir Based Regimens in Antiretroviral Therapy Experienced HIV-1 Patients: A Meta-Analysis and Meta-Regression of Randomized Controlled Clinical Trials

Background

The development of tipranavir and darunavir, second generation non-peptidic HIV protease inhibitors, with marked improved resistance profiles, has opened a new perspective on the treatment of antiretroviral therapy (ART) experienced HIV patients with poor viral load control. The aim of this study was to determine the virologic response in ART experienced patients to tipranavir-ritonavir and darunavir-ritonavir based regimens.

Methods and Findings

A computer based literature search was conducted in the databases of HINARI (Health InterNetwork Access to Research Initiative), Medline and Cochrane library. Meta-analysis was performed by including randomized controlled studies that were conducted in ART experienced patients with plasma viral load above 1,000 copies HIV RNA/ml. The odds ratios and 95% confidence intervals (CI) for viral loads of <50 copies and <400 copies HIV RNA/ml at the end of the intervention were determined by the random effects model. Meta-regression, sensitivity analysis and funnel plots were done. The number of HIV-1 patients who were on either a tipranavir-ritonavir or darunavir-ritonavir based regimen and achieved viral load less than 50 copies HIV RNA/ml was significantly higher (overall OR = 3.4; 95% CI, 2.61– 4.52) than the number of HIV-1 patients who were on investigator selected boosted comparator HIV-1 protease inhibitors (CPIs-ritonavir). Similarly, the number of patients with viral load less than 400 copies HIV RNA/ml was significantly higher in either the tipranavir-ritonavir or darunavir-ritonavir based regimen treated group (overall OR = 3.0; 95% CI, 2.15 – 4.11). Meta-regression showed that the viral load reduction was independent of baseline viral load, baseline CD4 count and duration of tipranavir-ritonavir or darunavir-ritonavir based regimen.

Conclusions

Tipranavir and darunavir based regimens were more effective in patients who were ART experienced and had poor viral load control. Further studies are required to determine their consistent viral load suppression effect as the duration of treatment is more prolonged.