Weight Gain After Switch from Efavirenz-Based to Integrase Inhibitor-Based Regimens

Abstract

BackgroundIntegrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART) offers persons living with HIV a potent new treatment option. Recently, local HIV clinicians noted weight gain in patients who switched from daily, fixed-dose efavirenz/tenofovir disoproxil fumarate/emtricitabine (EFV/TDF/FTC) to fixed-dose dolutegravir/abacavir/lamivudine (DTG/ABC/3TC). To assess whether regimen switch was significantly associated with weight gain, we evaluated body weight over time among patients with sustained virologic suppression who switched from EFV/TDF/FTC to an INSTI-containing regimen, including DTG/ABC/3TC.MethodsWe analyzed data from adult patients on EFV/TDF/FTC for >=2 years with consistent plasma HIV-1 RNA <1000 copies/mL prior to date of switch (or date of sham switch for those who remained on EFV/TDF/FTC). All maintained HIV-1 RNA <1000 copies/mL for >=18 months post-switch. We assessed weight change over 18 months in patients switched to an INSTI-containing regimen or a protease inhibitor (PI)-containing regimen vs. those remaining on EFV/TDF/FTC over the same period. In a sub-group analysis, we compared patients switched to DTG/ABC/3TC vs. raltegravir- or elvitegravir-containing regimens. Linear mixed effects models assessed mean differences in weight over time, adjusting for baseline age, sex, race, CD4+ count and weight.ResultsAmong 495 patients, 136 switched to an INSTI-containing regimen, 34 switched to a PI-containing regimen, and 325 remained on EFV/TDF/FTC. Patients switched to an INSTI-containing regimen gained an average of 2.9 kilograms (kg) at 18 months compared with 0.9 kg among those continued on EFV/TDF/FTC (P = 0.003, Figure a), while those switched to a PI regimen gained 0.7 kg (P = 0.81, Figure b). Among INSTI regimens, those switched to DTG/ABC/3TC gained 5.3 kg at 18 months, which was more than raltegravir or elvitegravir regimens (P = 0.19, Figure c) and significantly more than those continued on EFV/TDF/FTC (P = 0.001, Figure d).ConclusionSwitching from daily, fixed-dose EFV/TDF/FTC to an INSTI-containing regimen among patients with virologic control was associated with weight gain at 18 months. This weight gain was particularly profound among those switching to DTG/ABC/3TC.Disclosures All authors: No reported disclosures.

Weight gain among treatment‐naïve persons with HIV starting integrase inhibitors compared to non‐nucleoside reverse transcriptase inhibitors or protease inhibitors in a large observational cohort in the United States and Canada

“…Among patients receiving INSTI‐based regimens, these findings corroborate our prior report from a smaller Southeastern US cohort in which we described greater weight gain associated with DTG‐based ART regimen use [14], as well as reports from other observational cohorts [15‐17]. Moreover similar disparities in weight gain by initial ART regimen type were noted in a recent 48‐week, open‐label, randomized trial conducted in South Africa comparing EFV/TDF/FTC versus DTG with TDF/FTC or with TAF/FTC, which reported greater increases over 48 weeks in weight and truncal fat among DTG compared to EFV recipients, particularly among persons also receiving TAF.…”

“…In a cohort from Brazil, PWH receiving RAL‐based regimens were sevenfold more likely to become obese (BMI ≥ 30kg/m 2 ) compared to those receiving NNRTI‐ or PI‐based regimens [13]. In other observational studies, INSTI‐based regimens generally, and particularly DTG‐based ART regimens [14‐17], were also associated with greater weight gain. In the prospective AIDS Clinical Trial Group (ACTG) study A5257, the use of RAL with tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) as an initial ART regimen was associated with greater increases in waist circumference and increased odds of a >10% weight gain at 96 weeks, compared to ART regimens including ritonavir‐boosted darunavir or ritonavir‐boosted atazanavir, each combined with TDF/FTC [18,19].…”

Switch to dolutegravir is well tolerated in Thais with HIV infection

“…The mean weight gain of 2.3kg (3.7%) over 48 weeks was noticed by participants and was tolerated by all. A recent study reported a weight gain of 5.3kg in 18 months among participants who were virologically suppressed and mostly Caucasian and who switched from an EFV‐based regimen to DTG . However, this was not observed in other DTG trials of ART‐naïve or–experienced participants .…”

“…Neuropsychiatric AEs including headache, dizziness, sleep disturbances, mood disturbances, suicidal ideation and cognitive problems were reported. Unintentional weight gain was also described . Recently, an observational study in Botswana showed a higher rate of neural tube defects among infants born to women taking DTG during conception at 0.9% versus 0.1% in those taking other antiretroviral drugs .…”

New Drugs for NASH and HIV Infection: Great Expectations for a Great Need

“…( 28 ) Similar findings were described in experienced PLWH switching to INSTIs. ( 29 ) Nevertheless, metabolic consequences of weight gain after INSTI initiation are still controversial, and whether this will affect the risk of NAFLD in PLWH is unclear (Fig. 1).…”