The Cost-Effectiveness of Dolutegravir in Combination with Tenofovir and Lamivudine for HIV Therapy: A Systematic Review

Figures & data

Table 1 PICO for Search Term of Systematic Review

PICO Criteria	Main Concept	Synonyms/Abbreviations/More Specific Concepts
P – Problem	HIV	Human Immunodeficiency Virus; AIDS; Acquired Immune Deficiency Syndrome
I/E– Intervention/ Exposure	Dolutegravir (DTG)	Combination of tenofovir- lamivudine-DTG
C – Comparison	Efavirenz (EFV)	Combination of tenofovir-lamivudine-EFV
O – Outcome	Cost-effectiveness	Cost effectiveness; cost; cost saving; cost-effective

Table 2 Study Characteristics

Author	Year	Country	Title	Objective	Conclusion
Zheng et al^Citation19	2018	India	The cost-effectiveness and budgetary impact of a DTG-based regimen as first-line treatment of HIV infection in India.	This study used to examine the potential cost-effectiveness and budgetary impact of a DTG-based first line ART. strategy in India	A generic DTG-based regimen is likely to be cost-effective and should be recommended for the first-line treatment of HIV infection in India.
Phillips et al^Citation20	2018	Sub-Saharan Africa	Cost-effectiveness of public-health policy options in the presence of pretreatment NNRTI drug resistance in sub-Saharan Africa: a modelling study.	The objective of this research was to assess the efficacy and cost-effectiveness of alternative public health responses in sub-Saharan African countries with a high prevalence of pretreatment drug resistance to NNRTIs.	The transition from efavirenz to dolutegravir formulations in adult ART initiators is expected to be effective and cost-effective in low-income settings, depending on NNRTI resistance.
Phillips et al^Citation21	2019	Sub-Saharan Africa	Risks and benefit of DTG-based antiretroviral drug regimen in sub-Saharan Africa: a modelling study.	The objective is to provide policymakers a quantitative assessment of the risks and benefits of alternative policies for DTG.	The benefits of transitioning to tenofovir, lamivudine and DTG outweighed the risks in a DALY framework.
Punekar et al^Citation22	2019	China	Improving access to antiretrovirals in China: Economic analyses of DTG in HIV-1 patients.	The purpose of this study was to compare the cost-effectiveness of DTG (DTG + TDF/3TC) to efavirenz (EFV+TDF/3TC) in treatment-naive and ritonavir – boosted lopinavir (LPV/r + TDF/3TC) in HIV-1-infected patients on first-line ART in China.	DTG + TDF/3TC provides higher response rates and QALYs at lower costs than currently available ARV regimens, and inclusion of dolutegravir in the National Free AIDS Antiretroviral Drug List may offer an additional option in tackling HIV in China.
Phillips et al^Citation23	2020	Sub-Saharan Africa	Updated assessment of risk and benefits of DTG versus EFV in new antiretroviral treatment initiators in sub-Saharan Africa: modelling to inform treatment guidelines.	This study provides updated modelling results in response to WHO’s request for the 2019 antiretroviral guidelines revision.	DTG-based ART is predicted to bring population health benefits and be cost-effective, supporting WHO’s recommendation as a preferred drug in ART initiators.

Figure 1 Article selection flow process.

Abbreviations: HIV, human immunodeficiency virus; WHO, World Health Organization; DTG, dolutegravir; ART, antiretroviral; QALY, quality-adjusted life years; ICER, incremental cost-effectiveness ratio.

Table 3 Modelling Method

Author	Year	Perspective	Time Horizon	Discounting Rate	Model	Sensitivity Analyses
Zheng et al^Citation19	2018	Public health	2 years, 5 years and lifetime	3%	The Cost-Effectiveness of Preventing AIDS Complications (CEPAC)- International model	One-way and multiway sensitivity analysis
Phillips et al^Citation20	2018	Public health	20 years	3%	Individual-based simulation model	Multiway sensitivity analysis
Phillips et al^Citation21	2019	Public health	20 years	3%	Individual-based simulation model	Multiway sensitivity analysis
Punekar et al^Citation22	2019	Public health	5 years	2.3%	Dynamic Markov model	Deterministic and probabilistic sensitivity analysis
Phillips et al^Citation23	2020	Public health	20 years	3%	Individual-based simulation model	Multiway sensitivity analysis

Table 4 Research Outcome

Author	Outcome
Zheng et al^Citation19	Dolutegravir+Efavirenz/Lamivudine increased life expectancy from 22.0 to 24.8 years increased 5 years survival from 76.7% to 83.0% compared to standard of care in India. A lifetime ICER of $130/YLS, which is less than 10% of GDP per capita.
Phillips et al^Citation20	First line dolutegravir for all ART initiator is the most cost effective with net DALY averted per year.
Phillips et al^Citation21	The value of net DALYs averted per year ranges from 30,000 to 85,000 for treatment with tenofovir, lamivudine, and DTG in all scenarios. Over 1–5 years, viral suppression decreased, but not significantly over 20 years.
Punekar et al^Citation22	DTG+TDF/3TC resulted the viral suppression rates 75.3% that was higher than comparator. In comparison to EFV +TDF/3TC, DTG +TDF/3TC resulted in 0.006 additional QALYs at a cost saving of RMB 467.
Phillips et al^Citation23	In women planning pregnancy, initiation with tenofovir, lamivudine, and dolutegravir averted more DALYs 83%, was cost-effective 87%, and showed net DALYs averted per year of 16,735. Pregnancy in women is predicted to benefit population health (10,990 DALYs averted per year) and be cost-effective ($2.9 million per year), resulting in a decrease in the overall population burden of disease of 16,735 net DALYs per year for a nation with a population size of 10 million adults. ART initiation with a DTG-based regimen was cost-effective in 87% of setting scenarios and robust in sensitivity analyses.

Table 5 Quality Appraisal of Included Studies

	Item	Guidance for Reporting	Zheng et al	Phillips et al (2017)	Phillips et al (2018)	Punekar et al	Phillips et al (2020)	Total
Title
Title	1	Identify the study as an economic evaluation and specify the interventions being compared	1	1	1	1	1	100%
ABSTRACT
Abstract	2	Provide a structured summary that highlights context, key methods, results and alternative analyses	1	1	1	1	1	100%
INTRODUCTION
Background and objectives	3	Give the context for the study, the study question and its practical relevance for decision making in policy or practice	1	1	1	1	1	100%
METHODS
Health economic analysis plan	4	Indicate whether a health economic analysis plan was developed and where available	1	1	1	1	1	100%
Study population	5	Describe characteristics of the study population (such as age range, demographics, socioeconomic, or clinical characteristics)	1	0.5	0.5	0.5	0.5	60%
Setting and location	6	Provide relevant contextual information that may influence findings	1	1	1	1	1	100%
Comparators	7	Describe the interventions or strategies being compared and why chosen	1	1	1	1	1	100%
Perspective	8	State the perspective(s) adopted by the study and why chosen	0.5	1	1	1	1	90%
Time horizon	9	State the time horizon for the study and why appropriate	1	1	1	1	1	100%
Discount rate	10	Report the discount rate(s) and reason chosen	1	1	1	1	1	100%
Selection of outcomes	11	Describe what outcomes were used as the measure(s) of benefit(s) and harm(s)	1	1	1	1	1	100%
Measurement of outcomes	12	Describe how outcomes used to capture benefit(s) and harm(s) were measured	1	1	1	1	1	100%
Valuation of outcomes	13	Describe the population and methods used to measure and value outcomes	0.5	0.5	0.5	0.5	0.5	50%
Measurement and valuation of resources and costs	14	Describe how costs were valued	1	1	1	1	1	100%
Currency, price date, and conversion	15	Report the dates of the estimated resource quantities and unit costs, plus the currency and year of conversion	1	1	0.5	1	0.5	80%
Rationale and description of model	16	If modelling is used, describe in detail and why used. Report if the model is publicly available and where it can be accessed	1	1	1	1	1	100%
Analytics and assumptions	17	Describe any methods for analyzing or statistically transforming data, any extrapolation methods, and approaches for validating any model used	0.5	1	1	0.5	1	80%
Characterizing heterogeneity	18	Describe any methods used for estimating how the results of the study vary for sub-groups	0	1	1	0	1	60%
Characterizing distributional effects	19	Describe how impacts are distributed across different individuals or adjustments made to reflect priority populations	0	1	1	0	1	60%
Characterizing uncertainty	20	Describe methods to characterize any sources of uncertainty in the analysis	1	0.5	0.5	1	0.5	70%
Approach to engagement with patients and others affected by the study	21	Describe any approaches to engage patients or service recipients, the general public, communities, or stakeholders (eg, clinicians or payers) in the design of the study	n/a	n/a	n/a	n/a	n/a	n/a
RESULTS
Study parameters	22	Report all analytic inputs (eg, values, ranges, references) including uncertainty or distributional assumptions	1	1	1	1	1	100%
Summary of main results	23	Report the mean values for the main categories of costs and outcomes of interest and summarize them in the most appropriate overall measure	1	1	1	1	0.5	90%
Effect of uncertainty	24	Describe how uncertainty about analytic judgments, inputs, or projections affect findings. Report the effect of choice of discount rate and time horizon, if applicable	1	1	1	1	1	100%
Effect of engagement with patients and others affected by the study	25	Report on any difference patient/service recipient, general public, community, or stakeholder involvement made to the approach or findings of the study	n/a	n/a	n/a	n/a	n/a	n/a
DISCUSSION
Study findings, limitations, generalizability, and current knowledge	26	Report key findings, limitations, ethical or equity considerations not captured, and how these could impact patients, policy, or practice	1	1	1	1	1	100%
OTHER RELEVANT INFORMATION
Source of funding	27	Describe how the study was funded and any role of the funder in the identification, design, conduct, and reporting of the analysis	1	1	1	1	1	100%
Conflict of interest	28	Report authors conflicts of interest according to journal or International Committee of Medical Journal Editors requirements	1	1	1	1	1	100%
Overall quality			86.5%	94.2%	92.3%	88.5%	84.6%

Zheng A, Kumarasamy N, Huang M, et al. The cost-effectiveness and budgetary impact of a dolutegravir-based regimen as first-line treatment of HIV infection in India. J Int Aids Soc. 2018; (3):e25085

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Phillips AN, Cambiano V, Nakagawa F, et al. Cost-effectiveness of public-health policy options in the presence of pretreatment NNRTI drug resistance in sub-Saharan Africa: a modelling study. The Lancet HIV. 2018;5(3):e146–e154. doi:10.1016/S2352-3018(17)30190-X

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Phillips AN, Venter F, Havlir D, et al. Risks and benefit of dolutegravir-based antiretroviral drug regimen in sub-Saharan Africa: a modelling study. Lancet HIV. 2019; 6(2):e116

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Punekar YS, Guo N, Tremblay G, Piercy J, Holbrook T, Young B Cost-effectiveness of public-health policy options in the presence of pretreatment NNRTI drug resistance in sub-Saharan Africa: a modelling study. Lancet HIV. 2018;5(3): e146

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Phillips AN, Bansi-Matharu L, Venter F, et al. Updated assessment of risk and benefits of dolutegravir versus efavirenz in new antiretroviral treatment initiators in sub-Saharan Africa: modelling to inform treatment guidelines. Lancet HIV. 2020; 7(3): e193–200.

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