Weight Changes With Integrase Strand Transfer Inhibitor Therapy in the Management of HIV Infection: A Systematic Review

Abstract

Objective: To describe weight changes with integrase strand transfer inhibitor (INSTI) therapy. Data Sources: A literature search was performed (through December 15, 2021) using the PubMed and CINAHL databases using the search terms: “integrase inhibitors,” “integrase strand transfer inhibitors,” and “weight.” Study Selection and Data Extraction: Studies were included that provided relevant information on weight or body mass index (BMI) changes on INSTI therapy. Controlled or observational studies comparing different INSTI therapies or compared INSTI therapy to another class of antiretroviral therapy were included. Data Synthesis: Forty-three articles met criteria for inclusion, and data are presented. Although some trials have observed similar weight gains between INSTI, protease inhibitor, and non-nucleoside inhibitor therapies, the increase appears to be greater with INSTI therapy, particularly during initiation of therapy. Risk factors for weight gain with INSTI therapy include female gender, lower CD4 count, and combined use of tenofovir alafenamide. Within the INSTI class, dolutegravir and bictegravir appear to have the greatest propensity for weight gain. Relevance to Patient Care and Clinical Practice: INSTI-based therapies are the preferred initial management of HIV infection. Discerning the factors contributing to weight changes on INSTI therapy and risks of associated health-related outcomes is important to both the management of weight gain and HIV medical management. Conclusions: Within the INSTI class, dolutegravir and bictegravir may be associated with the greatest risk for weight gain particularly when combined with tenofovir alafenamide. Further research is needed to determine mechanisms for observed weight changes and any contributions to clinically significant metabolic and cardiovascular adverse outcomes associated with INSTI therapy.

Efficacy, safety and tolerability of Biktarvy in HIV-1 infection: A scoping review

“…However, as the prevalence of obesity in PLWH continues to increase, further investigation into other weight gain mechanisms is necessary. 33,36 Importantly, no included studies reported on the development of metabolic syndrome, diabetes or cardiovascular complications. In addition to reporting on weight changes, future research should investigate these clinically important outcomes Of note, one study of patients switching from EVG/F/ TAF to B/F/TAF found a significant decrease in eGFR of 5 mL/min.…”

Six-month incidence of hypertension and diabetes among adults with HIV in Tanzania: A prospective cohort study

“…Our study was not suited to evaluate associations between incident hypertension and ART (95% of our participants were on the same dolutegravir-based regimen–TLD), however some studies in SSA have found an association between older NRTI, NNRTI and PI agents (namely zidovudine, stavudine, nevirapine, and lopinavir-ritonavir) and hypertension [ 28 , 29 ]. Moreover, the increasingly recognized associations between integrase inhibitors and obesity and other metabolic complications is of concern [ 37 , 38 ], as these conditions tend to predispose invidiuals to hypertension and atherosclerotic cardiovascular (ASCVD) disease possibly increasing cardiovascular-related morbidity and mortality. As > 90% of all PWH in SSA are currently on an integrase based regimen (including participants in our sample), and as HIV is a known independent risk factor for ASCVD-related events, this may be problematic [ 39 – 42 ].…”

Personalizing prevention: Advances in pharmacotherapy for HIV prevention

“…There is increasing evidence that INSTIs may be associated with weight gain. 45 At Week 96 in HPTN 083 and HPTN 084, those who received CAB-LA had gained a median of 2.1 and 4 kg, respectively, compared with 1 and 3 kg, respectively, for those who received FTC/TDF. 43,44 The clinical significance of this weight gain is unclear, and there is less data with CAB-LA compared with other…”

“…Other than ISRs, CAB‐LA appears to be well‐tolerated. There is increasing evidence that INSTIs may be associated with weight gain 45 . At Week 96 in HPTN 083 and HPTN 084, those who received CAB‐LA had gained a median of 2.1 and 4 kg, respectively, compared with 1 and 3 kg, respectively, for those who received FTC/TDF 43,44 .…”