Comparative efficacy, tolerability and safety of dolutegravir and efavirenz 400mg among antiretroviral therapies for first-line HIV treatment: A systematic literature review and network meta-analysis

Kanters, Steve; Vitória, Marco; Zoratti, Michael J.; Doherty, Meg; Penazzato, Martina; Rangaraj, Ajay; Ford, Nathan; Thorlund, Kristian; Anis, Aslam H.; Karim, Mohammad Ehsanul; Mofenson, Lynne; Zash, Rebecca; Calmy, Alexandra; Kredo, Tamara; Bansback, Nick

doi:10.1016/j.eclinm.2020.100573

Cited by 79 publications

(72 citation statements)

References 41 publications

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“…DTG was recommended following compelling evidences from many studies on its effectiveness in achieving viral suppression, relative safety and it´s relative cheaper cost [ 11 , 13 - 15 ]. Both DTG and other older ARV has been associated with long term cardiometabolic toxicities [ 14 , 16 - 18 ]. However, not very much have been reported on the effectiveness and safety of the relatively DTG in Cameroon.…”

Section: Resultsmentioning

confidence: 99%

Research priorities for accelerating the achievement of three 95 HIV goals in Cameroon: a consensus statement from the Cameroon HIV Research Forum (CAM-HERO)

Dzudié¹,

Tchounga²,

Ajeh³

et al. 2021

Pan Afr Med J

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Introduction the Treat-All remains the globally endorsed approach to attain the 95-95-95 targets and end the AIDS pandemic by 2030, but requires some country-level contextualization. In Cameroon, the specific research agenda to inform strategies for improving HIV policy was yet to be defined. Methods under the patronage of the Cameroon Ministry of health, researchers, policy makers, implementing partners, and clinicians from 13 institutions, used the Delphi method to arrive at a consensus of HIV research priorities. The process had five steps: 1) independent literature scan by 5 working groups; 2) review of the initial priority list; 3) appraisal of priorities list in a larger group; 4) refinement and consolidation by a consensus group; 5) rating of top research priorities. Results five research priorities and corresponding research approaches, resulted from the process. These include: 1) effectiveness, safety and active toxicity monitoring of new and old antiretrovirals; 2) outcomes of Antiretroviral Therapy (ART) with focus in children and adolescents; 3) impact of HIV and ART on aging and major chronic diseases; 4) ART dispensation models and impact on adherence and retention; 5) evaluations of HIV treatment and prevention programs. Conclusion the research priorities resulted from a consensus amongst a multidisciplinary team and were based on current data about the pandemic and science to prevent, treat, and ultimately cure HIV. These priorities highlighted critical areas of investigation with potential relevance for the country, funders, and regulatory bodies.

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Section: Resultsmentioning

confidence: 99%

Research priorities for accelerating the achievement of three 95 HIV goals in Cameroon: a consensus statement from the Cameroon HIV Research Forum (CAM-HERO)

Dzudié¹,

Tchounga²,

Ajeh³

et al. 2021

Pan Afr Med J

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“…This study also aimed to understand the potential impact of including individual patient data for the particular application of comparing the therapeutic landscape of anchor treatments in firstline ART for the treatment of HIV. To this end, it was reassuring to find that the conclusions reached through the evidence synthesis supplemented by the individual patient data did not lead to changes that would have impacted the WHO change in guidelines that took place in December 2018 and subsequently in 2020 [39,40]. The possibility that the limited impact of IPD on study results are due in part to the relatively small number of patients in the network providing IPD was investigated through a separate simulation study [41].…”

Section: Discussionmentioning

confidence: 99%

Comparing the use of aggregate data and various methods of integrating individual patient data to network meta-analysis and its application to first-line ART

Kanters

Karim

Thorlund

et al. 2021

BMC Med Res Methodol

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Background The 2018 World Health Organization HIV guidelines were based on the results of a network meta-analysis (NMA) of published trials. This study employed individual patient-level data (IPD) and aggregate data (AgD) and meta-regression methods to assess the evidence supporting the WHO recommendations and whether they needed any refinements. Methods Access to IPD from three trials was granted through ClinicalStudyDataRequest.com (CSDR). Seven modelling approaches were applied and compared: 1) Unadjusted AgD network meta-analysis (NMA) – the original analysis; 2) AgD-NMA with meta-regression; 3) Two-stage IPD-AgD NMA; 4) Unadjusted one-stage IPD-AgD NMA; 5) One-stage IPD-AgD NMA with meta-regression (one-stage approach); 6) Two-stage IPD-AgD NMA with empirical-priors (empirical-priors approach); 7) Hierarchical meta-regression IPD-AgD NMA (HMR approach). The first two were the models used previously. Models were compared with respect to effect estimates, changes in the effect estimates, coefficient estimates, DIC and model fit, rankings and between-study heterogeneity. Results IPD were available for 2160 patients, representing 6.5% of the evidence base and 3 of 24 edges. The aspect of the model affected by the choice of modeling appeared to differ across outcomes. HMR consistently generated larger intervals, often with credible intervals (CrI) containing the null value. Discontinuations due to adverse events and viral suppression at 96 weeks were the only two outcomes for which the unadjusted AgD NMA would not be selected. For the first, the selected model shifted the principal comparison of interest from an odds ratio of 0.28 (95% CrI: 10.17, 0.44) to 0.37 (95% CrI: 0.23, 0.58). Throughout all outcomes, the regression estimates differed substantially between AgD and IPD methods, with the latter being more often larger in magnitude and statistically significant. Conclusions Overall, the use of IPD often impacted the coefficient estimates, but not sufficiently as to necessitate altering the final recommendations of the 2018 WHO Guidelines. Future work should examine the features of a network where adjustments will have an impact, such as how much IPD is required in a given size of network.

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“…A secondary analysis was performed to test for interaction between baseline weight and outcomes by ART regimen. Given our primary interest in understanding how pregnancy outcomes may be impacted by the increasing use of DTG (which is replacing EFV in most HIV treatment programmes globally) [28,29] we chose to limit this analysis to TDF/XTC/DTG versus TDF/XTC/EFV. We fit adjusted log binomial models as described above to evaluate each individual outcome by baseline weight, and included ART regimen (DTG/EFV) and an interaction term (for DTG/EFV).…”

Section: Methodsmentioning

confidence: 99%

Maternal weight and birth outcomes among women on antiretroviral treatment from conception in a birth surveillance study in Botswana

et al. 2021

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Introduction Antiretrovirals such as dolutegravir (DTG) and tenofovir alafenamide (TAF) have been associated with excessive weight gain. The objective of this study was to understand the potential impact of ART‐associated weight gain on pregnancy outcomes among women living with HIV. Methods Using data from the Tsepamo birth outcomes surveillance study in Botswana, we evaluated the relationship between maternal weight (and weight gain) and severe birth outcomes (very preterm delivery <32 weeks, very small for gestational age (SGA) <3rd percentile, perinatal death), macrosomia (birthweight > 4000 g) and maternal hypertension. We estimated the relative risk of each outcome by baseline weight (first weight in pregnancy <24 weeks) and second trimester average weekly weight gain (kg/week from 12 ± 2 to 24 ± 2 weeks) using log binomial regression and evaluated effect modification by ART regimen (DTG vs. Efavirenz (EFV)). Results Of 22,828 women on ART at conception with singleton deliveries between August 2014 and April 2020, 16,300 (71.4%) had a weight measured <24 weeks’ gestation (baseline weight) and 4437 (19.2%) had weight measured both at 12 (±2) weeks and 24 (±2) weeks, allowing second trimester weight gain calculation. Compared to women with baseline weight 60 to 70 kg, low baseline weight (<50 kg) was associated with increased risk of very preterm delivery (aRR 1.30, 95% CI 1.03, 1.65) and very SGA (aRR1.96, 95% CI 1.69, 2.28). High baseline weight (>90 kg) was associated with increased risk of macrosomia (aRR 3.24, 95% CI 2.36, 4.44) and maternal hypertension (aRR 1.79, 95% CI 1.62, 1.97). Baseline weight was not associated with stillbirth or early neonatal death. For all outcomes, second trimester weight gain showed weaker associations than did baseline weight. Duration of pre‐pregnancy ART (years) was associated with higher baseline weight for DTG but not for EFV, and the risk of maternal hypertension by baseline weight category was higher for DTG than EFV for all strata. Conclusions ART regimens associated with weight gain may reduce the number of women at risk for certain severe adverse pregnancy outcomes associated with low weight but increase the number at risk of macrosomia and maternal hypertension. Further research could determine whether weight‐based ART treatment strategies improve maternal and child health.

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Comparative efficacy, tolerability and safety of dolutegravir and efavirenz 400mg among antiretroviral therapies for first-line HIV treatment: A systematic literature review and network meta-analysis

Cited by 79 publications

References 41 publications

Research priorities for accelerating the achievement of three 95 HIV goals in Cameroon: a consensus statement from the Cameroon HIV Research Forum (CAM-HERO)

Research priorities for accelerating the achievement of three 95 HIV goals in Cameroon: a consensus statement from the Cameroon HIV Research Forum (CAM-HERO)

Comparing the use of aggregate data and various methods of integrating individual patient data to network meta-analysis and its application to first-line ART

Maternal weight and birth outcomes among women on antiretroviral treatment from conception in a birth surveillance study in Botswana

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