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Adverse Events During ART and Implications for Treatment: Key Data From Summer 2021
  • CME
  • CE

Eric S. Daar, MD
Released: September 22, 2021

INSTIs and Insulin Resistance

Switch to INSTI and Weight Gain and Insulin Resistance

One of the main concerns about metabolic changes such as weight gain is the potential development of insulin resistance. In addition, one question we must ask is whether there is a relationship between INSTI-associated weight gain and insulin resistance.

This was explored in an observational, longitudinal, matched-cohort study of weight and BMI changes associated with switching to an INSTI-based regimen.8 The study enrolled ART-experienced PWH without diabetes at the Modena HIV Metabolic Clinic in Italy. Participants were matched for baseline BMI and duration of observation before any regimen switches.

A subset of the population continued the original regimen (the INSTI-naive group), and another subset switched to an INSTI-based regimen (the INSTI switch group). Hence, this is not a randomized, controlled trial; this is observational data.

Among those enrolled, 70% were male, and the median BMI was 23. Of importance, these patients had generally high CD4 cell counts (median: 552 cells/mm3), and the overwhelming majority (85.5%) had undetectable HIV-1 RNA.

Anthropometrics and Cardiometabolic Conditions at Time of Switch and Follow-up

In the overall population, those who switched to an INSTI experienced a significantly greater increase in weight and BMI vs those who continued their baseline regimen. In addition, there was a higher incidence of metabolic syndrome at follow-up in the switch group. 

The primary analysis, however, was the incidence of insulin resistance in the overall population, and there was no difference at follow-up regardless of switching to an INSTI or remaining INSTI naive.

Anthropometrics and Cardiometabolic Conditions at Time of Switch and Follow-up in PWH Without IR at T1

Next, they looked at the subgroup of participants without insulin resistance at the time of switch. Among 465 patients who continued their baseline regimen and 169 who switched to an INSTI, there was no meaningful difference in median weight, weight change, or BMI at the time of follow-up. This is unlike the overall population, which was more heterogeneous.

Moreover, if we look at the cardiometabolic conditions, at follow-up, there was a significantly lower rate of insulin resistance amongst those who switched to the INSTI vs those who stayed on their regimen.

Taken together, the implication is that switching to an INSTI has no increased risk of cardiometabolic alterations, regardless of whether a person has insulin resistance. This is despite some probable bias in the population, such as that patients who have underlying metabolic conditions may be more likely to be switching to an INSTI-based regimen.

Moreover, although switching to an INSTI-based regimen is associated with weight gain and a BMI increase in the overall population, in the subset of patients without insulin resistance at the time of switch, there actually was a significantly lower risk of developing insulin resistance.

Taken together, the implication is that switching to an INSTI has no increased risk of cardiometabolic alterations, regardless of whether a person has insulin resistance. This is despite some probable bias in the population, such as that patients who have underlying metabolic conditions may be more likely to be switching to an INSTI-based regimen.

Moreover, although switching to an INSTI-based regimen is associated with weight gain and a BMI increase in the overall population, in the subset of patients without insulin resistance at the time of switch, there actually was a significantly lower risk of developing insulin resistance.

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