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. 2022 May 12:48:101412.
doi: 10.1016/j.eclinm.2022.101412. eCollection 2022 Jun.

Evidence synthesis evaluating body weight gain among people treating HIV with antiretroviral therapy - a systematic literature review and network meta-analysis

Steve Kanters  1   2 , Francoise Renaud  3 , Ajay Rangaraj  3 , Kenneth Zhang  2 , Eve Limbrick-Oldfield  2 , Monica Hughes  4 , Nathan Ford  3 , Marco Vitoria  3
Affiliations

Evidence synthesis evaluating body weight gain among people treating HIV with antiretroviral therapy - a systematic literature review and network meta-analysis

Steve Kanters et al. EClinicalMedicine. .

Abstract

Background: This systematic review aimed to compare body weight gain associated outcomes over time between dolutegravir (DTG)-based antiretroviral (ART) regimens to other ART regimens, to compare tenofovir alafenamide (TAF)-based regimens, and to evaluate the associated prognostic factors.

Methods: Systematic searches of MEDLINE, Embase, and CENTRAL for RCTs and observational studies comparing ART regimens were conducted on 13 September 2021. Outcomes of interest included: change in body weight, body mass index (BMI), waist circumference; and risk of hyperglycaemia and diabetes. Network meta-analyses were conducted at 12, 24, 48, 96 and 144 weeks using two networks differentiated by 3rd agents and backbone agents.

Findings: The review identified 113 publications reporting on 73 studies. DTG-based regimens led to statistically higher weight gains than efavirenz-based regimens at all time points (mean difference: 1·99 kg at 96 weeks; 95% credible interval: 0·85-3·09) and was higher over time than low-dose efavirenz-, elvitegravir-, and rilpivirine-based regimens. They were comparable to raltegravir-, bictegravir- and atazanavir-based regimens. For backbones, TAF led to higher weight gain relative to tenofovir disoproxil fumarate (TDF), abacavir, and zidovudine. Prognostic factor analysis showed both low CD4 cell count and high HIV RNA viral load at baseline were consistently associated with higher weight gain, while sex was an effect modifier to African origins.

Interpretation: DTG-based regimens lead to larger average weight gains than some other ART regimens and TAF leads to larger average weight gains than all other backbone antiretrovirals. Further research is needed to better understand long-term outcomes and their relationship to other metabolic outcomes.

Funding: The WHO Global HIV, Hepatitis and Sexually Transmitted Infections Programmes.

Keywords: Body weight gain; Dolutegravir; HIV; Network meta-analysis; Prognostic factors; Systematic review; Tenofovir alafenamide.

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Conflict of interest statement

Steve Kanters, Eve Limbrick-Oldfield, and Kenneth Zhang are employees at RainCity Analytics. All other authors have nothing to declare.

Figures

Fig 1
Figure 1
Evidence network of all studies included in the (A) primary network and (B) NRTI network. Each circle represents a treatment of interest. Each line represents the existence of comparative evidence between the two connected treatments. The names on each line represent studies providing the evidence. In network (A), the colours represent treatment classes: integrase inhibitors in gold, NNRTIs in black and PIs in green. BIC: bictegravir; BB: Back bone (mixed); DTG: dolutegravir; EFV: efavirenz; EVG/c: elvitegravir/cobicistat; RAL: raltegravir; DOR: Doravirine; DRV/r: Ritonavir-boosted darunavir; ATV/r: Ritonavir-boosted atazanavir; LPV/r: Ritonavir-boosted lopinavir; 3TC: Lamivudine; TAF: tenofovir alafenamide; TDF: Tenofovir disoproxil fumarate; ABC: Abacavir; AZT: Zidovudine.
Fig 2
Figure 2
Flow diagram for the systematic literature review.
Fig 3
Figure 3
Forest plots for change in weight over time comparing (a) DTG to integrase inhibitors, EFV and other regimens and (b) TAF to other NRTIs according to a series of network meta-analyses. BIC: bictegravir; BB: Back bone (mixed); DTG: dolutegravir; EFV: efavirenz; EVG/c: elvitegravir/cobicistat; RAL: raltegravir; DOR: Doravirine; DRV/r: Ritonavir-boosted darunavir; 3TC: Lamivudine; TAF: tenofovir alafenamide; TDF: Tenofovir disoproxil fumarate; ABC: Abacavir; AZT: Zidovudine; RCT: Randomized controlled trials; NMA: Network meta-analysis. Points represent estimated relative treatment effects for body weight gain using network meta-analyses based on the full evidence base (green circle) and on RCTs only (black diamond). The horizontal lines represent 95% credible intervals for the estimates using the full evidence base. Credible intervals not crossing the dashed vertical line represent a statistically significant difference between the two treatments.
Fig 4
Figure 4
Overview of the prognostic factors analysis for weight change while on antiretroviral therapy. US: United States; ZA: South Africa; KE: Kenya; BE: Belgium; IT: Italy; CM: Cameroon; AU: Australia; CN: China; PL: Poland.
See this image and copyright information in PMC

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