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Switch to Integrase Drug Incites BMI Gain But Perhaps Improved "Fat Quality"
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HIV Drug Therapy/Glasgow 2020, October 5-8, 2020
Mark Mascolini
In a 4-year study of 108 HIV-positive people who gained 5% or more weight, those who switched to an integrase inhibitor (InSTI) had bigger jumps in body mass index (BMI) than those who never took an InSTI [1]. But a greater decline in visceral adipose tissue (VAT) density in switchers, the researchers proposed, may signal an improvement in "fat tissue quality."
Over the past several years, reports of weight gains when switching to InSTIs have accumulated, raising concern about the overall health of people taking these powerful antiretrovirals. Researchers working at the Modena (Italy) HIV Metabolic Clinic (MHMC) and colleagues at other centers wondered whether fat quantity and density differed in people who gain weight when swapping a suppressive antiretroviral regimen for one including an InSTI.
The Modena team noted that people classified as obese by BMI above 30 kg/m2 constitute a "remarkably heterogeneous" group and that people with similar BMI or body weight "can have substantially different comorbidities and levels of health risk." They suggested that fat density may provide a proxy for fat quality. Lower fat density, they proposed, reflects larger adipocytes (fat cells) and increased fat content. Higher fat density, on the other hand, reflects greater inflammation and fibrosis.
The study compared antiretroviral-treated MHMC members who never took an InSTI and those who switched to an InSTI. Matching these groups for age, sex, and BMI, the researchers assessed fat quantity and fat quality. Measures of fat quantity were weight, total lean mass, and total fat mass (by DXA scan) and VAT, subcutaneous adipose tissue (SAT), epicardial adipose tissue (EAT), and liver-to-spleen density ratio (by CT scan). Measures of fat quality (all assessed by CT scan) were VAT density, SAT density, EAT density, and psoas muscle density.
Baseline groups included 207 people who never took an InSTI and 211 who switched to an InSTI from a non-InSTI regimen. The groups did not differ significantly in age (average about 50), proportions of men (about 71%), BMI (about 23.5 kg/m2), waist circumference (about 87 cm), or any of the fat measures listed in the previous paragraph. Compared with the InSTI-naive group, those who switched to an InSTI had a lower median nadir CD4 count (150 vs 210, P < 0.001), longer median HIV duration (228.5 vs 191.5 months, P = 0.001), lower (worse) average CD4/CD8 ratio (0.74 vs 0.89, P = 0.001), and lower median current CD4 count (559 vs 623, P = 0.002).
In the InSTI-naive group, 51 of 207 people (25%) gained more than 5% in weight, while 57 of 211 (27%) in the InSTI-switch group gained more than 5%. Follow-up averaged 4 years in the InSTI-naive group and 4.5 years in the switch group (P = 0.36).
Only 11.8% of the naive group and 14% of the switch group were initially obese (difference not significant, P = 0.95), but people in the switch group gained significantly more BMI (2.47 vs 1.9 kg/m2, P = 0.006). Weight gain through follow-up was similar in the naive group and the switch group, whether measured as either total lean mass or total fat. But fat gain drove weight gain in both groups (+5.5 and +6.2 kg in InSTI-naive and switchers).
Both groups had high VAT, with little difference between groups (average 165.7 cm2 in naive, 166.1 cm2 in switchers (P = 0.82). InSTI switchers gained more SAT than the InSTI-naive group, and that difference approached statistical significance (+61.3 vs +45.5 cm2, P = 0.06). The switch group also lost significantly more VAT density than the naive group (-5.8 vs -2 HU, P < 0.001), and the researchers suggested that difference may indicate improved fat quality in switchers. SAT density fell by a similar measure in the switch and naive groups (-4.15 vs -3.7 HU, P = 0.22), which the researchers surmised may reflect improved fat quality in both groups.
The Modena collaborators concluded that among people who gain at least 5% in weight during antiretroviral therapy, those who switch to an InSTI gained more BMI (mainly because of jumps in SAT) than those who remained naive to InSTIs. But a greater drop in VAT density in InSTI switchers, they proposed, "does not suggest a metabolic abnormal fat gain but we may hypothesize an improvement in fat tissue quality."
Reference
1. Guaraldi G, Draisci S, Milic J, et al. Fat distribution and density in people living with HIV with ≥5% weight gain. HIV Drug Therapy/Glasgow 2020, October 5-8, 2020. Abstract O111.
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