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ART Safety Data: Summer 2021

CE / CME

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

Pharmacists: 0.75 contact hour (0.075 CEUs)

Physicians: Maximum of 0.75 AMA PRA Category 1 Credit™

Nurses: 0.75 Nursing contact hour

Released: September 22, 2021

Expiration: September 21, 2022

CME/CE Information

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DRIVE-AHEAD: DOR/3TC/TDF vs EFV/FTC/TDF in Treatment-Naive Adults at Week 192

The first study of interest is DRIVE-AHEAD, in which the primary endpoint compared once-daily doravirine (DOR)/3TC/tenofovir disoproxil fumarate (TDF) vs efavirenz (EFV)/emtricitabine (FTC)/TDF at Week 48 in treatment-naive patients with no underlying resistance. A secondary endpoint compared outcomes at Week 96.1

There was then an open-label extension where patients who were randomized to the EFV/FTC/TDF arm were given open-label DOR/3TC/TDF at Week 96 with follow-up through Week 192, the latter being presented in the current analysis.

The primary efficacy data have been presented previously, and these regimens demonstrated similar efficacy, with some potential safety advantages of the DOR arm, particularly with neuropsychiatric AEs.2,3

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DRIVE-AHEAD: Week 192 Neuropsychiatric AEs

At IAS 2021, we saw the extended 192-week neuropsychiatric AE data for those who continued their original DOR/3TC/TDF vs those who switched after approximately 2 years of follow-up to the open-label extension.

The data demonstrate similar overall outcomes for any neuropsychiatric event: dizziness, sleep disorders and disturbances, altered sensorium, depression and suicide/self-injury, and psychosis and psychotic disorders.

Among participants who switched to DOR/3TC/TDF, there was a modest numerical increase in the percentage of some neuropsychiatric AEs. However, this is consistent with most studies that look at ART switch, because switching from a stable, generally well-tolerated regimen usually puts patients at more risk for new AEs.

The results were quite similar and supportive of earlier analyses: Overall, DOR/3TC/TDF was associated with few neuropsychiatric abnormalities.

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DRIVE-AHEAD: Week 192 Metabolic Changes

We know that many of our therapeutics have some effect on lipids and weight. We also know from earlier analyses of DRIVE-AHEAD that EFV has some metabolic consequences, particularly regarding lipids, but that DOR had appeared to be more lipid neutral.2,3

Therefore, at Week 192, the investigators looked at changes in fasting lipids in those who continued DOR/3TC/TDF out to 192 weeks and found no clinically meaningful changes in low-density lipoprotein (LDL), non–high-density lipoprotein (HDL), total cholesterol, triglycerides, or HDL.

Next, they looked at the population of patients who switched to DOR/3TC/TDF in the open-label extension. They compared data from Day 1 to Week 96 (before the switch) with data from Week 96-192 (after the switch). As expected based on previous data, the switch was associated with improvement in lipids, including reductions in LDL, non-HDL, total cholesterol, triglycerides, and HDL. Once again, this data suggest a potential benefit of switching. above and beyond the neuropsychiatric complications.

Regarding weight outcomes, most participants gained weight over the course of observation, which is commonly seen in trials of patients initiating ART. There was virtually no difference in the weight increases between the EFV and DOR arms through 96 weeks. It is notable that much of the attention for weight gain has been in the context of INSTIs and TAF, which were not part of either regimen.

Among those who switched from the EFV-based regimen to the DOR-based regimen at Week 96, there was a small increase in weight over the course of follow-up, with a median increase of 3 kg in those who switched vs 2 kg in those who were originally randomized to DOR. Again, this was a small difference, and the CIs were overlapping, supporting earlier data that these regimens do not seem to be associated with a marked increase in weight above and beyond what would be expected with general initiation of therapy with longitudinal follow-up for several years.

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