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Quadruple versus triple combination antiretroviral therapies for treatment naive people with HIV: systematic review and meta-analysis of randomised controlled trials.
BMJ 2019; 366:l4179BMJ

Abstract

OBJECTIVE

To evaluate the effects of four drug (quadruple) versus three drug (triple) combination antiretroviral therapies in treatment naive people with HIV, and explore the implications of existing trials for clinical practice and research.

DESIGN

Systematic review and meta-analysis of randomised controlled trials.

DATA SOURCES

PubMed, EMBASE, CENTRAL, Web of Science, and the Cumulative Index to Nursing and Allied Health Literature from March 2001 to December 2016 (updated search in PubMed and EMBASE up to June 2018); and reference lists of eligible studies and related reviews.

STUDY SELECTION

Randomised controlled trials comparing quadruple with triple combination antiretroviral therapies in treatment naive people with HIV and evaluating at least one effectiveness or safety outcome.

REVIEW METHODS

Outcomes of interest included undetectable HIV-1 RNA, CD4 T cell count, virological failure, new AIDS defining events, death, and severe adverse effects. Random effects meta-analyses were conducted.

RESULTS

Twelve trials (including 4251 people with HIV) were eligible. Quadruple and triple combination antiretroviral therapies had similar effects on all relevant effectiveness and safety outcomes, with no point estimates favouring quadruple therapy. With the triple therapy as the reference group, the risk ratio was 0.99 (95% confidence interval 0.93 to 1.05) for undetectable HIV-1 RNA, 1.00 (0.90 to 1.11) for virological failure, 1.17 (0.84 to 1.63) for new AIDS defining events, 1.23 (0.74 to 2.05) for death, and 1.09 (0.89 to 1.33) for severe adverse effects. The mean difference in CD4 T cell count increase between the two groups was -19.55 cells/μL (-43.02 to 3.92). In general, the results were similar, regardless of the specific regimens of combination antiretroviral therapies, and were robust in all subgroup and sensitivity analyses.

CONCLUSION

In this study, effects of quadruple combination antiretroviral therapy were not better than triple combination antiretroviral therapy in treatment naive people with HIV. This finding lends support to current guidelines recommending the triple regimen as first line treatment. Further trials on this topic should be conducted only when new research is justified by adequate systematic reviews of the existing evidence. However, this study cannot exclude the possibility that quadruple cART would be better than triple cART when new classes of antiretroviral drugs are made available.

Authors+Show Affiliations

Division of Epidemiology, Jockey Club School of Public Health and Primary Care, Chinese University of Hong Kong, Hong Kong, China.Division of Epidemiology, Jockey Club School of Public Health and Primary Care, Chinese University of Hong Kong, Hong Kong, China.School of Public Health (Shenzhen), Sun Yat-Sen University, Shenzhen, China. Kirby Institute, University of New South Wales, Sydney, Australia.Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.Department of Infectious Disease, Guangzhou Eighth People's Hospital, Guangzhou, China.Division of Infectious Diseases, Department of Internal Medicine, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan. School of Public Health, National Yang-Ming University, Taipei, Taiwan.Division of Epidemiology, Jockey Club School of Public Health and Primary Care, Chinese University of Hong Kong, Hong Kong, China zyang@cuhk.edu.hk.Division of Epidemiology, Jockey Club School of Public Health and Primary Care, Chinese University of Hong Kong, Hong Kong, China. Shenzhen Key Laboratory for Health Risk Analysis, Shenzhen Research Institute of the Chinese University of Hong Kong, Shenzhen, China.

Pub Type(s)

Journal Article
Meta-Analysis
Systematic Review

Language

eng

PubMed ID

31285198

Citation

Feng, Qi, et al. "Quadruple Versus Triple Combination Antiretroviral Therapies for Treatment Naive People With HIV: Systematic Review and Meta-analysis of Randomised Controlled Trials." BMJ (Clinical Research Ed.), vol. 366, 2019, p. l4179.
Feng Q, Zhou A, Zou H, et al. Quadruple versus triple combination antiretroviral therapies for treatment naive people with HIV: systematic review and meta-analysis of randomised controlled trials. BMJ. 2019;366:l4179.
Feng, Q., Zhou, A., Zou, H., Ingle, S., May, M. T., Cai, W., ... Tang, J. (2019). Quadruple versus triple combination antiretroviral therapies for treatment naive people with HIV: systematic review and meta-analysis of randomised controlled trials. BMJ (Clinical Research Ed.), 366, p. l4179. doi:10.1136/bmj.l4179.
Feng Q, et al. Quadruple Versus Triple Combination Antiretroviral Therapies for Treatment Naive People With HIV: Systematic Review and Meta-analysis of Randomised Controlled Trials. BMJ. 2019 Jul 8;366:l4179. PubMed PMID: 31285198.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Quadruple versus triple combination antiretroviral therapies for treatment naive people with HIV: systematic review and meta-analysis of randomised controlled trials. AU - Feng,Qi, AU - Zhou,Aoshuang, AU - Zou,Huachun, AU - Ingle,Suzanne, AU - May,Margaret T, AU - Cai,Weiping, AU - Cheng,Chien-Yu, AU - Yang,Zuyao, AU - Tang,Jinling, Y1 - 2019/07/08/ PY - 2019/05/13/accepted PY - 2019/7/10/entrez PY - 2019/7/10/pubmed PY - 2019/7/12/medline SP - l4179 EP - l4179 JF - BMJ (Clinical research ed.) JO - BMJ VL - 366 N2 - OBJECTIVE: To evaluate the effects of four drug (quadruple) versus three drug (triple) combination antiretroviral therapies in treatment naive people with HIV, and explore the implications of existing trials for clinical practice and research. DESIGN: Systematic review and meta-analysis of randomised controlled trials. DATA SOURCES: PubMed, EMBASE, CENTRAL, Web of Science, and the Cumulative Index to Nursing and Allied Health Literature from March 2001 to December 2016 (updated search in PubMed and EMBASE up to June 2018); and reference lists of eligible studies and related reviews. STUDY SELECTION: Randomised controlled trials comparing quadruple with triple combination antiretroviral therapies in treatment naive people with HIV and evaluating at least one effectiveness or safety outcome. REVIEW METHODS: Outcomes of interest included undetectable HIV-1 RNA, CD4 T cell count, virological failure, new AIDS defining events, death, and severe adverse effects. Random effects meta-analyses were conducted. RESULTS: Twelve trials (including 4251 people with HIV) were eligible. Quadruple and triple combination antiretroviral therapies had similar effects on all relevant effectiveness and safety outcomes, with no point estimates favouring quadruple therapy. With the triple therapy as the reference group, the risk ratio was 0.99 (95% confidence interval 0.93 to 1.05) for undetectable HIV-1 RNA, 1.00 (0.90 to 1.11) for virological failure, 1.17 (0.84 to 1.63) for new AIDS defining events, 1.23 (0.74 to 2.05) for death, and 1.09 (0.89 to 1.33) for severe adverse effects. The mean difference in CD4 T cell count increase between the two groups was -19.55 cells/μL (-43.02 to 3.92). In general, the results were similar, regardless of the specific regimens of combination antiretroviral therapies, and were robust in all subgroup and sensitivity analyses. CONCLUSION: In this study, effects of quadruple combination antiretroviral therapy were not better than triple combination antiretroviral therapy in treatment naive people with HIV. This finding lends support to current guidelines recommending the triple regimen as first line treatment. Further trials on this topic should be conducted only when new research is justified by adequate systematic reviews of the existing evidence. However, this study cannot exclude the possibility that quadruple cART would be better than triple cART when new classes of antiretroviral drugs are made available. SN - 1756-1833 UR - https://www.unboundmedicine.com/medline/citation/31285198/Quadruple_versus_triple_combination_antiretroviral_therapies_for_treatment_naive_people_with_HIV:_systematic_review_and_meta-analysis_of_randomised_controlled_trials L2 - http://www.bmj.com/cgi/pmidlookup?view=long&pmid=31285198 DB - PRIME DP - Unbound Medicine ER -