Association between integrase strand transfer inhibitor (INSTIs) use with insulin resistance and incident diabetes mellitus in persons living with HIV: A systematic review and meta-analysis protocol

Mulindwa, Frank; Kamal, Habiba; Castelnuovo, Barbara; Bollinger, Robert C.; Schwarz, Jean-Marc; Brussealers, Nele

doi:10.1371/journal.pone.0264792

Cited by 4 publications

(3 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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 ].…”

Section: Discussionmentioning

confidence: 99%

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

Sakita,

O’Leary,

Prattipati

et al. 2023

PLOS Glob Public Health

View full text Add to dashboard Cite

Data describing the incidence of hypertension and diabetes among people with HIV in sub-Saharan Africa remain sparse. In this study, adults with HIV were enrolled from a public clinic in Moshi, Tanzania (September 2020—March 2021). At enrollment, a survey was administered to collect information on comorbidities and medication use. Each participant’s blood pressure and point-of-care glucose were measured. Baseline hypertension was defined by blood pressure ≥140/90 mmHg or self-reported hypertension at enrollment. Baseline diabetes was defined by self-reported diabetes or hyperglycemia (fasting glucose ≥126 mg/dl or random glucose ≥200 mg/dl) at enrollment. At 6-month follow-up, participants’ blood pressure and point-of-care glucose were again measured. Incident hypertension was defined by self-report of new hypertension diagnosis or blood pressure ≥140/90 mmHg at follow-up in a participant without baseline hypertension. Incident diabetes was defined as self-report of new diabetes diagnosis or measured hyperglycemia at follow-up in a participant without baseline diabetes. During the study period, 477 participants were enrolled, of whom 310 did not have baseline hypertension and 457 did not have baseline diabetes. At six-month follow-up, 51 participants (95% CI: 38, 67) had new-onset hypertension, corresponding to an incidence of 33 new cases of hypertension per 100 person-years. Participants with incident hypertension at 6-month follow-up were more likely to have a history of alcohol use (90.2% vs. 73.7%, OR = 3.18, 95% CI:1.32–9.62, p = 0.008) and were older (mean age = 46.5 vs. 42.3, p = 0.027). At six-month follow-up, 8 participants (95% CI: 3, 16) had new-onset diabetes, corresponding to an incidence of 3 new cases of diabetes per 100 person-years. In conclusion, the incidence of elevated blood pressure and diabetes among Tanzanians with HIV is higher than what has been reported in high-income settings.

show abstract

Section: Discussionmentioning

confidence: 99%

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

Sakita,

O’Leary,

Prattipati

et al. 2023

PLOS Glob Public Health

View full text Add to dashboard Cite

show abstract

“…The protocol for this systematic review is registered on International Prospective Register of Systematic Reviews database ( CRD42021273040 ) and published. 31 This study is being reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. 32 The link to the study dataset is listed in the online supplemental material (SD).…”

Section: Methodsmentioning

confidence: 99%

Association between integrase strand transfer inhibitor use with insulin resistance and incident diabetes mellitus in persons living with HIV: a systematic review and meta-analysis

Mulindwa

Kamal

Castelnuovo

et al. 2023

BMJ Open Diab Res Care

Self Cite

View full text Add to dashboard Cite

Whether integrase strand transfer inhibitors (INSTIs) are associated with a higher risk of incident type 2 diabetes mellitus (DM) than other antiretroviral therapies (ART) needs to be established.MEDLINE, Embase, Web of Science, and ClinicalTrials.gov registries were searched for studies published between 1 January 2000 and 15 June 2022. Eligible studies reported incident DM or mean changes in insulin resistance measured by Homeostatic Model for Insulin Resistance (HOMA-IR) in patients on INSTIs compared with other ARTs. We performed random-effects meta-analyses to obtain pooled relative risks (RRs) with 95% CIs.A total of 16 studies were pooled: 13 studies meta-analyzed for incident diabetes with a patient population of 72 404 and 3 for changes in HOMA-IR. INSTI therapy was associated with a lower risk of incident diabetes in 13 studies (RR 0.80, 95% CI 0.67 to 0.96, I2=29%), of which 8 randomized controlled trials demonstrated a 22% reduced risk (RR 0.88, 95% CI 0.81 to 0.96, I2=0%). INSTIs had a lower risk compared with non-nucleoside reverse transcriptase inhibitors (RR 0.75, 95% CI 0.63 to 0.89, I2=0%) but similar to protease inhibitor-based therapy (RR 0.78, 95% CI 0.61 to 1.01, I2=27%). The risk was lower in studies with longer follow-up (RR 0.70, 95% CI 0.53 to 0.94, I2=24%) and among ART-naïve patients (RR 0.78, 95% CI 0.65 to 0.94, I2=3%) but increased in African populations (RR 2.99, 95% CI 2.53 to 3.54, I2=0%).In conclusion, exposure to INSTIs was not associated with increased risk of DM, except in the African population. Stratified analyses suggested reduced risk among ART-naïve patients and studies with longer follow-up.International Prospective Register of Systematic Reviews (PROSPERO) registration number: CRD42021273040.

show abstract

“…We explored the relationship of INSTI use with incident diabetes in PWH at population level in an earlier meta-analysis [13], [14]. In that analysis, we demonstrated that the risk of incident DM is actually reduced with INSTI use compared to protease inhibitors and NNRTIs apart from African populations which were largely under-represented.…”

Section: Introductionmentioning

confidence: 99%

Dolutegravir use over 48 weeks is not associated with worsening insulin resistance and pancreatic beta cell function in a cohort of HIV-infected Ugandan adults

Mulindwa,

Castelnuovo,

Brusselaers

et al. 2023

AIDS Res Ther

Self Cite

View full text Add to dashboard Cite

Background The Uganda Ministry of Health issued restrictive guidelines on the use of dolutegravir (DTG) in persons stratified to have a heightened risk of diabetes mellitus. This followed multiple reports of persons with HIV (PWH) presenting with accelerated hyperglycemia after a few weeks to months of exposure to DTG. Having demonstrated a low incidence of diabetes mellitus and improving blood glucose trajectories in a cohort of ART naïve Ugandan PWH on DTG, we sought to determine whether the observed improvement in blood glucose did not mask background compensated insulin resistance. Methods In this analysis, 63 patients underwent serial oral glucose tolerance tests over 48 weeks. Using fasting serum insulin and glucose, we calculated insulin resistance and pancreatic beta cell function by homeostatic modelling (HOMA IR and HOMA%β respectively). Absolute mean changes between baseline and post-baseline blood glucose, pancreatic beta cell function and insulin resistance were computed by subtracting each post-baseline value from the baseline value and compared using student t-test. Multiple linear regression models were used to determine the factors associated with changes in pancreatic beta cell function and insulin resistance. Results Of the 63 participants, 37 (58%) were female. Median age was 31 (IQR: 28–37). Despite a trend towards an initial increase in both HOMA IR and HOMA%β at 12 weeks followed by a decline through 36 weeks to 48 weeks, the HOMA IR and HOMA%β at 48 weeks were not significantly different from baseline i.e. (difference in mean HOMA IR from baseline: 0.14, 95%CI: -0.46, 0.733, p = 0.648) and (difference in mean HOMA %β from baseline: 6.7, 95%CI: -13.4, 26.8, p = 0.506) respectively. Conclusion We demonstrated insignificant changes in both insulin resistance and pancreatic beta cell function in clinically stable young adult Ugandan PWH on dolutegravir for 48 weeks. We add to the body of evidence demonstrating glucose metabolic safety of dolutegravir in ART naïve patients. Ugandan guidelines should reconsider restricting DTG initiation in ART naive adults at high risk for diabetes.

show abstract

Association between integrase strand transfer inhibitor (INSTIs) use with insulin resistance and incident diabetes mellitus in persons living with HIV: A systematic review and meta-analysis protocol

Cited by 4 publications

References 13 publications

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

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

Association between integrase strand transfer inhibitor use with insulin resistance and incident diabetes mellitus in persons living with HIV: a systematic review and meta-analysis

Dolutegravir use over 48 weeks is not associated with worsening insulin resistance and pancreatic beta cell function in a cohort of HIV-infected Ugandan adults

Contact Info

Product

Resources

About