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Abacavir-based triple nucleoside regimens for maintenance therapy in patients with HIV

  1. Mario Cruciani1,*,
  2. Carlo Mengoli2,
  3. Giovanni Serpelloni3,
  4. Saverio G Parisi2,
  5. Marina Malena4,
  6. Oliviero Bosco4

Editorial Group: Cochrane HIV/AIDS Group

Published Online: 5 JUN 2013

Assessed as up-to-date: 10 JUL 2012

DOI: 10.1002/14651858.CD008270.pub2


How to Cite

Cruciani M, Mengoli C, Serpelloni G, Parisi SG, Malena M, Bosco O. Abacavir-based triple nucleoside regimens for maintenance therapy in patients with HIV. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD008270. DOI: 10.1002/14651858.CD008270.pub2.

Author Information

  1. 1

    ULSS 20 Verona, Center of Community Medicine and Infectious Diseases Service, Verona, Italy

  2. 2

    Università di Padova, Department of Histology, Microbiology and Medical Biotechnology, PADOVA, Italy

  3. 3

    ULSS 20 Verona, Dipartimento delle Dipendenze, 37135 Verona, Italy

  4. 4

    ULSS 20 Verona, Center of Community Medicine, 37135 Verona, Italy

*Mario Cruciani, Center of Community Medicine and Infectious Diseases Service, ULSS 20 Verona, Via Germania, 20, Verona, 37135, Italy. crucianimario@virgilio.it.

Publication History

  1. Publication Status: New
  2. Published Online: 5 JUN 2013

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Characteristics of included studies [ordered by year of study]
Clumeck 2001

MethodsProspective, multicenter, open-label, comparative, randomised study


ParticipantsHIV-1 infected patients treated with successful first-line therapy (2NRTI plus PI); mostly on 1st line PI ART, but around 10 % with previous 2 NRTI or monotherapy (AZT)


Interventionstriple NRTI combination (zidovudine/lamivudine/abacavir) vs continuation of 2NRTI plus PI (indinavir, nelfinavir, ritonavir, saquinavir)


Outcomestreatment failure, defined as virologic failure (HIV RNA >400 cp/ml) or premature discontinuation of randomised study treatment; virologic suppression <50 cp/ml; evolution of CD4; change in metabolic parameters, development of adverse events


Characteristics of Included studies


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskpatients were randomly allocated

Allocation concealment (selection bias)Unclear riskInsufficient information to permit judgment of ‘Low risk’ or ‘High risk’

Blinding of participants and personnel (performance bias)
All outcomes
High riskNo blinding, and the review authors judge that some of the outcomes are likely to be influenced by lack of blinding

Blinding of outcome assessment (detection bias)
All outcomes
High riskNo blinding, and the review authors judge that some of the outcomes are likely to be influenced by lack of blinding

Incomplete outcome data (attrition bias)
All outcomes
Low riskOutcome data available from all randomised participants analysed in the group to which they were allocated. ITT analysis.

Selective reporting (reporting bias)Low riskThe study protocol is available and all of the study’s pre-specified (primary and secondary) outcomes that are of interest in the review have been reported in the pre-specified way

Other biasLow riskThe study appears to be free of other sources of bias.

Opravil 2002

MethodsProspective, multicenter, open-label, comparative, randomised study


ParticipantsHIV-1 infected patients treated with successful first-line therapy with 2NRTI plus PI (indinavir, nelfinavir, ritonavir, saquinavir, saquinavir/r)


InterventionsPatients were randomised to continuing their current PI-containing antiretroviral regimen or to switch to triple NRTI combination (co formulation of zidovudine/lamivudine plus abacavir or trizivir®)


OutcomesTreatment failure, defined as virologic failure (HIV RNA >200 cp/ml), any change of randomised study treatment, or loss to follow-up; tolerability; change in metabolic parameters.


Characteristics of Included studies


NotesPatients who have the reverse transcriptase 215 mutation were excluded; study included patients ( ̴ 50 %) with sub-optimal previous treatment (e.g., mono- or dual NRTI treatment)


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskCentralized randomisation

Allocation concealment (selection bias)Low riskcentral allocation

Blinding of participants and personnel (performance bias)
All outcomes
High riskNo blinding, and the review authors judge that some of the outcomes are likely to be influenced by lack of blinding

Blinding of outcome assessment (detection bias)
All outcomes
High riskNo blinding, and the review authors judge that some of the outcomes are likely to be influenced by lack of blinding

Incomplete outcome data (attrition bias)
All outcomes
Low riskOutcome data available from all randomised participants analysed in the group to which they were allocated. ITT analysis.

Selective reporting (reporting bias)Low riskThe study protocol is available and all of the study’s pre-specified (primary and secondary) outcomes that are of interest in the review have been reported in the pre-specified way

Other biasLow riskThe study appears to be free of other sources of bias.

Maggiolo 2003

MethodsProspective, randomised, single centre, Open-Label study.


ParticipantsHIV-1 infected patients treated with successful therapy with 2NRTI plus PI (indinavir, nelfinavir, saquinavir); 20 % only were on first line treatment, but not specified previous treatment


InterventionsPatients were randomised to either continued therapy with their current PI-containing antiretroviral regimen or to the same regimen with abacavir or efavirenz, substituted for the PI.


OutcomesTreatment failure, defined as virologic failure (HIV RNA >500 cp/ml) or premature discontinuation of randomised study treatment; virologic suppression <50 cp/ml; evolution of CD4; change in metabolic parameters.


Characteristics of Included studies


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskpatients were randomly allocated

Allocation concealment (selection bias)Unclear riskInsufficient information to permit judgment of ‘Low risk’ or ‘High risk’

Blinding of participants and personnel (performance bias)
All outcomes
High riskNo blinding, and the review authors judge that some of the outcomes are likely to be influenced by lack of blinding

Blinding of outcome assessment (detection bias)
All outcomes
Low riskNo blinding, but particular attention paid to limiting potential judgment biases

Incomplete outcome data (attrition bias)
All outcomes
Low riskOutcome data available from all randomised participants analysed in the group to which they were allocated. ITT analysis.

Selective reporting (reporting bias)Low riskThe study protocol is available and all of the study’s pre-specified (primary and secondary) outcomes that are of interest in the review have been reported in the pre-specified way

Other biasLow riskThe study appears to be free of other sources of bias.

Katlama 2003

MethodsProspective, multicenter, open-label, randomised study


ParticipantsHIV-1 infected patients treated with successful first-line therapy :2NRTI plus PI (61 %; 21 % indinavir + combivir®), 2NRTI plus NNRTI, 3NRTI


Interventionsco formulated zidovudine/lamivudine/abacavir vs continuation of triple-therapy regimen (2NRTI plus PI, 2NRTI plus NNRTI, 3NRTI)


OutcomesTreatment failure, defined as virologic failure (HIV RNA >540 cp/ml) or premature discontinuation of randomised study treatment; virologic suppression <50 cp/ml; evolution of CD4; change in metabolic parameters, development of adverse events


Characteristics of Included studies


NotesPatients with previous NRTI mono-therapy not included


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskcentrally randomised

Allocation concealment (selection bias)Low riskcentral allocation

Blinding of participants and personnel (performance bias)
All outcomes
High riskNo blinding, and the review authors judge that some of the outcomes are likely to be influenced by lack of blinding

Blinding of outcome assessment (detection bias)
All outcomes
High riskNo blinding, and the review authors judge that some of the outcomes are likely to be influenced by lack of blinding

Incomplete outcome data (attrition bias)
All outcomes
Low riskOutcome data available from all randomised participants analysed in the group to which they were allocated. ITT analysis.

Selective reporting (reporting bias)Low riskThe study protocol is available and all of the study’s pre-specified (primary and secondary) outcomes that are of interest in the review have been reported in the pre-specified way

Other biasLow riskThe study appears to be free of other sources of bias.

NEFA Study

MethodsProspective, multicenter, open-label, comparative, randomised study


ParticipantsHIV-1 infected patients treated with successful ART regimen containing a PI and 2 NRTI


InterventionsPatients were randomised to switch from their current PI-containing antiretroviral regimen to the same double NRTI regimen in combination with abacavir, nevirapine or efavirenz as substituted for the PI.


OutcomesDeath, progression to AIDS, virologic failure (RNA >200 cp/ml); CD4 count, incidence of side effects, metabolic changes.


Characteristics of Included studies


NotesStudy included patients with sub-optimal previous treatment (e.g., mono- or dual NRTI treatment)


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskCentralized randomizations

Allocation concealment (selection bias)Low riskEach patient's identification number and treatment group assigned at the coordinating centre after the centre had received the randomizations form.

Blinding of participants and personnel (performance bias)
All outcomes
High riskNo blinding, and the review authors judge that some of the outcomes are likely to be influenced by lack of blinding

Blinding of outcome assessment (detection bias)
All outcomes
High riskNo blinding, and the review authors judge that some of the outcomes are likely to be influenced by lack of blinding

Incomplete outcome data (attrition bias)
All outcomes
Low riskOutcome data available from all randomised participants analysed in the group to which they were allocated. ITT analysis.

Selective reporting (reporting bias)Low riskThe study protocol is available and all of the study’s pre-specified (primary and secondary) outcomes that are of interest in the review have been reported in the pre-specified way

Other biasLow riskThe study appears to be free of other sources of bias.

Keiser 2005

MethodsProspective, Randomized, Multicenter, Open-Label study


ParticipantsHIV-1 infected experienced patients treated with successful therapy with 2NRTI plus PI (indinavir, nelfinavir, saquinavir, amprenavir)


InterventionsPatients were randomised to either continued therapy with their current PI-containing antiretroviral regimen or to the same regimen with abacavir, substituted for the PI(s).


OutcomesThe primary endpoint was the change in fasting total cholesterol from baseline at Week 28.The secondary endpoints were the proportion of subjects with plasma HIV-1 RNA <50 copies/mL and the proportion of subjects with plasma HIV-1 RNA <400 copies/mL at each scheduled post-baseline assessment


Characteristics of Included studies


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskpatients were randomly allocated

Allocation concealment (selection bias)Unclear riskInsufficient information to permit judgment of ‘Low risk’ or ‘High risk’

Blinding of participants and personnel (performance bias)
All outcomes
High riskNo blinding, and the review authors judge that some of the outcomes are likely to be influenced by lack of blinding

Blinding of outcome assessment (detection bias)
All outcomes
High riskNo blinding,and the review authors judge that some of the outcomes are likely to be influenced by lack of blinding

Incomplete outcome data (attrition bias)
All outcomes
Low riskOutcome data available from all randomised participants analysed in the group to which they were allocated. ITT analysis.

Selective reporting (reporting bias)Low riskThe study protocol is available and all of the study’s pre-specified (primary and secondary) outcomes that are of interest in the review have been reported in the pre-specified way

Other biasLow riskThe study appears to be free of other sources of bias.

Bonjoch 2005

MethodsProspective, multicenter, open-label, comparative, randomised, non-inferiority study


ParticipantsHIV-1 infected patients treated with successful first-line therapy. Up to 89% of the patients in ABC group and 94% of the subjects in nelfinavir group were receiving PIs at inclusion in the study. Overall, the most frequent PIs were nelfinavir (35%), ritonavir-boosted indinavir (21.6%), and unboosted indinavir (17.2%). Most frequent NRTI strategies were: lamivudine + stavudine (45%) and zidovudine + lamivudine (20%).


Interventionscoformulated zidovudine/lamivudine/abacavir vs coformulated zidovudine/lamivudine + nevirapine


Outcomesvirologic suppression <200 cp/ml at 48 wks; virologic suppression <50 cp/ml; evolution of CD4; change of lipid metabolism


Characteristics of Included studies


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskMulticenter, open label, blinded, centrally randomised

Allocation concealment (selection bias)Low riskcentrally randomised

Blinding of participants and personnel (performance bias)
All outcomes
High riskNo blinding, and the review authors judge that some of the outcomes are likely to be influenced by lack of blinding

Blinding of outcome assessment (detection bias)
All outcomes
High riskNo blinding, and the review authors judge that some of the outcomes are likely to be influenced by lack of blinding

Incomplete outcome data (attrition bias)
All outcomes
Low riskOutcome data available from all randomised participants analysed in the group to which they were allocated. ITT analysis.

Selective reporting (reporting bias)Low riskThe study protocol is available and all of the study’s pre-specified (primary and secondary) outcomes that are of interest in the review have been reported in the pre-specified way

Other biasLow riskThe study appears to be free of other sources of bias.

Sprenger 2010

MethodsProspective, multicenter, open-label, comparative, randomised study


ParticipantsHIV-1 infected patients treated with successful first-line therapy (2NRTI plus lopinavir/ritonavir)


InterventionsPatients were randomised to continuing their current PI-containing antiretroviral regimen or to switch to triple NRTI combination (co formulation of zidovudine/lamivudine/ abacavir)


OutcomesPrimary Outcome Measures: Plasma HIV-RNA < 400 cop/ml at week 96 for the Intent- To-Treat (ITT). Secondary Outcome Measures: HIV-RNA <50 cop at week 96
HIV-RNA <400 and <50 cop/ml at week 48 Time to virological failure Immunological efficacy at week 48 and 96 measured by absolute change from baseline in CD4 cell counts. Duration of change in CD4 cell count from baseline to >200, Proportion of subjects experiencing one or more predefined values of fasting glucose and triglycerides, LDL and LDL/HDL ratio. Development of adverse events


Characteristics of Included studies


NotesStudy data refer to the interim analysis at 48 wks


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskon a 1:1 basis by computer generated allocation

Allocation concealment (selection bias)Unclear riskInsufficient information to permit judgement of ‘Low risk’ or ‘High risk’

Blinding of participants and personnel (performance bias)
All outcomes
High riskNo blinding, and the review authors judge that some of the outcomes are likely to be influenced by lack of blinding

Blinding of outcome assessment (detection bias)
All outcomes
High riskNo blinding, and the review authors judge that some of the outcomes are likely to be influenced by lack of blinding

Incomplete outcome data (attrition bias)
All outcomes
Low riskOutcome data available from all randomised participants analysed in the group to which they were allocated. ITT analysis.

Selective reporting (reporting bias)Low riskThe study protocol is available and the interim analysis at 48 wks reports the outcomes that are of interest in the review in the pre-specified way

Other biasLow riskThe study appears to be free of other sources of bias.

 
Characteristics of excluded studies [ordered by year of study]

StudyReason for exclusion

Staszewsky 2001A randomised trial in naive patients of abacavir/lamivudine/zidovudine vs indinavir/lamivudine/zidovudine

Moyle 2002A retrospective study of pretreated patients who switched to a simplified regiment with triple NRTI regimen containing abacavir

Chiesa 2003Observational cohort study of patients with undetectable HIV RNA on PI containing treatment switched to a combination containing nevirapine, efavirenz or abacavir.

Matheron 2003A randomised trial in naive patients of abacavir/lamivudine/zidovudine vs nelfinavir/lamivudine/zidovudine

Vibhagool 2004Randomized trial of abacavir/lamivudine/zidovudine vs indinavir/lamivudine/zidovudine in ART-naive patients

Ibarra Barrueta 2004A retrospective study of pretreated patients who switched to a simplified regimen with trizivir®

Gulick 2004A randomised trial of triple-nucleoside regimens vs efavirenz containing regimens as a first line treatment in naive patients

Orkin 2004A randomised trial comparing a three- and four-drug HAART regimen in first-line therapy (QUAD study)

Cozzi-lepri 2006A multi cohort prospective observational study comparing abacavir and efavirenz as the third drug used in combination with a background therapy regimen of 2 nucleoside reverse-transcriptase inhibitors in patients with initially suppressed viral loads

Kumar 2006A randomised trial of trizivir, combivir/nelfinavir, and lamivudine/stavudine/nelfinavir in naive patients

Abgrall 2006A cohort study of patients with undetectable HIV RNA who switched from a first PI containing treatment to a combination containing efavirenz, nevirapine or abacavir

Abgrall 2007A cohort study of patients who switched from a first unsuccessful PI containing treatment to a combination containing efavirenz, nevirapine or abacavir

Palma 2007A cohort of paediatric patients switched from protease inhibitor-based HAART to triple nucleoside regimens

Wolbers 2007An observational cohort study of patients switched to triple NRTI combination with abacavir after successful previous treatment with a PI or NNRTI containing combination treatment

Kumar 2009RCT of initial anti-retroviral therapy with triple NRTI combination vs atazanavir/lamivudine/zidovudine

Munderi 2010A randomised trial in naive patients of abacavir/lamivudine/zidovudine vs nevirapine/lamivudine/zidovudine

Bommenel 2011A cohort study of patients who continued on a virologically successful first-line boosted protease inhibitor (PI)-containing combination antiretroviral therapy regimen or who switched to a PI-free cART including efavirenz, nevirapine or abacavir.

 
Comparison 1. Abacavir vs PI continuation or NNRTI

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Failure (overall)81606Risk Ratio (M-H, Random, 95% CI)0.88 [0.74, 1.04]

    1.1 ABC vs PI
6908Risk Ratio (M-H, Random, 95% CI)0.80 [0.62, 1.03]

    1.2 ABC vs NNRTI
3698Risk Ratio (M-H, Random, 95% CI)0.99 [0.79, 1.24]

 2 Discontinuation for adverse events81597Risk Ratio (M-H, Random, 95% CI)0.68 [0.44, 1.07]

    2.1 ABC vs PI
6899Risk Ratio (M-H, Random, 95% CI)0.77 [0.39, 1.53]

    2.2 ABC vs NNRTI
3698Risk Ratio (M-H, Random, 95% CI)0.63 [0.34, 1.18]

 3 Virologic failure81587Risk Ratio (M-H, Random, 95% CI)1.39 [0.95, 2.02]

    3.1 ABC vs PI
6899Risk Ratio (M-H, Random, 95% CI)1.49 [0.72, 3.08]

    3.2 ABC vs NNRTI
3688Risk Ratio (M-H, Random, 95% CI)1.32 [0.89, 1.97]

 4 Death41044Risk Ratio (M-H, Fixed, 95% CI)1.80 [0.43, 7.61]

    4.1 ABC vs PI
3579Risk Ratio (M-H, Fixed, 95% CI)3.87 [0.44, 34.22]

    4.2 ABC vs NNRTI
1465Risk Ratio (M-H, Fixed, 95% CI)0.71 [0.07, 6.74]

 5 Death & AIDS related events41044Risk Ratio (M-H, Fixed, 95% CI)1.66 [0.62, 4.42]

    5.1 ABC vs PI
3579Risk Ratio (M-H, Fixed, 95% CI)1.44 [0.41, 5.04]

    5.2 ABC vs NNRTI
1465Risk Ratio (M-H, Fixed, 95% CI)2.12 [0.43, 10.38]

 6 Any Adverse Events3837Risk Ratio (M-H, Random, 95% CI)0.92 [0.73, 1.15]

    6.1 ABC vs PI
2372Risk Ratio (M-H, Random, 95% CI)1.01 [0.80, 1.27]

    6.2 ABC vs NNRTI
1465Risk Ratio (M-H, Random, 95% CI)0.75 [0.61, 0.94]

 7 Rate of patients with Viral Load < 50 cp/ml5774Risk Ratio (M-H, Random, 95% CI)1.04 [0.92, 1.18]

    7.1 ABC vs PI continuation
4640Risk Ratio (M-H, Random, 95% CI)1.05 [0.91, 1.21]

    7.2 ABC vs NNRTI
1134Risk Ratio (M-H, Random, 95% CI)0.98 [0.76, 1.27]

 
Comparison 2. ABC vs NNRTI

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Failure (overall)3Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    1.1 ABC vs Nevirapine
2364Risk Ratio (M-H, Fixed, 95% CI)0.99 [0.74, 1.32]

    1.2 ABC vs efavirenz
2369Risk Ratio (M-H, Fixed, 95% CI)1.01 [0.72, 1.42]

 2 Discontinuation for Adverse Events3Risk Ratio (M-H, Random, 95% CI)Subtotals only

    2.1 ABC vs Nevirapine
2364Risk Ratio (M-H, Random, 95% CI)0.63 [0.28, 1.42]

    2.2 ABC vs Efavirenz
2369Risk Ratio (M-H, Random, 95% CI)0.54 [0.21, 1.40]

 3 Virologic failure3Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    3.1 ABC vs Nevirapine
2364Risk Ratio (M-H, Fixed, 95% CI)1.11 [0.71, 1.75]

    3.2 ABC vs Efavirenz
2369Risk Ratio (M-H, Fixed, 95% CI)2.76 [1.21, 6.31]

 
Summary of findings for the main comparison.

Abacavir-containing triple nucleoside simplification compared with PI or NNRTI containing regimens for HIV infection

Patient or population: HIV-infected adult patients treated with a PI-containing regimen  with undetectable viral load

Settings: Treatment simplification in patients who achieved viral suppression

Intervention: Triple nucleoside combination (Abacavir-Zidovudine-Lamivudine)

Comparison: PI or NNRTI containing ART regimens

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

PI or NNRTI regimensTriple Nucleoside Regimen

Failure (overall)330 per 1000284 per 1000
(212 to 369)
RR 0.88 (0.74, 1.04)1606
(8)
⊕⊕⊕⊝
moderate

Discontinuation for adverse events177 per 1000117 per 1000
(86-157)
RR 0.68 (0.44, 1.07)1597
(8)
⊕⊕⊕⊝
moderate

Virologic failure77 per 1000102 per 1000
(64 to 160)
RR 1.39 (0.95, 2.02)1587
(8)
⊕⊕⊕⊝
moderate

Death and AIDS related events13 per 100025 per 1000

(12 to 49)
RR 1.66 (0.62, 4.42)1044

(4)
⊕⊕⊝⊝

Low quality

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk Ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 
Table 1. Baseline characteristics of included studies

StudyViral load (copies/ml)Duration (months) of  last ART treatment*CD4 cells/mm3*Age in yrs*Male (%)

Clumeck 2001Undetectability since initiation of therapy and <50 at screening20  in each arm504 (ABC) vs 507 (PI)28 in each arm78 (PI) vs 87 (ABC)

Opravil 2002<400 for ≥6 months and <50 at screening27 (PI) vs 21 (ABC)513 (PI) vs 507 (ABC)41 (PI) vs 28 (ABC)76 (PI) vs 79 (ABC)

Katlama 2003<400 since initiation of therapy and < 50 within 14 days of study entry27 (ABC) vs 24482 (ABC) vs 50440 (ABC) vs 3780 (ABC) vs 83

Maggiolo 2003<50 over the last 6 months and at screening21 ( ABC), 20.6 (EFV), 21 (PI)600(ABC),  597 (EFV),  598 (PI)**36.1 (ABC),  36.7 (EFV), 37.7 (PI)**33 (ABC), 29 (EFV), 39 (PI)

NEFA study<200 for ≥6 months30 (ABC), 31(EFV), 29 (NVP)544 (ABC), 558 (EFV), 508 (NVP)40 (ABC), 38 (EFV), 39 (NVP)76 (ABC), 75 (EFV), 77 (NVP)

Keiser 20052 most recently tests <400 and <50 at screeningns; on a well-tolerated PI-containing

ART for >3 months
551 (ABC) vs 531 (PI)**43 (ABC) vs 42 (PI)46 (ABC) vs 47 (PI)

Bonjoch 2005<200 for ≥6 monthsns530 (ABC) vs  544 (NVP)39 in each arm82

Sprenger 20102 tests <50 between wks 12 and wks 24 before randomisation≥6 months310 (ABC) vs  350 (PI)43.1 (ABC) vs 40.3 (PI)82 (ABC) vs 88 (PI)

 * data are medians; ** data are means. Legenda: PI= protease inhibitors; ABC=abacavir; EFV= efavirenz; NVP= nevirapine; ns= not stated
 
Table 2. Summary estimates and heterogeneity for selected outcomes

OutcomeRisk Ratio95 % CIP value for effect estimatesHeterogeneity (I2 )P value for heterogeneity

Overall Failure 0.880.74-1.040.1517 %0.29

-ABC vs PI0.800.62-1.030.0829 %0.22

-ABC vs NNRTI0.990.79-1.240.950 %0.69

Discontinuation for adverse events 0.680.44-1.070.0957 %0.02

-ABC vs PI0.770.39-1.530.4665 %0.01

-ABC vs NNRTI0.630.34-1.180.1554 %0.11

Virologic failure 1.390.95-2.020.0918 %0.28

-ABC vs PI1.490.72-3.080.2839 %0.14

-ABC vs NNRTI1.320.89-1.970.170 %0.47

Death & AIDS related events 1.660.62-4.420.310 %0.65

-ABC vs PI1.440.41-5.040.570 %0.48

-ABC vs NNRTI2.120.43-10.380.35Not applicable 

 ABC= abacavir containing triple nucleoside combination; PI= protease inhibitor; NNRTI= non-nucleoside