Tenofovir disoproxil fumarate/emtricitabine plus ritonavir-boosted lopinavir or cobicistat-boosted elvitegravir as a single-tablet regimen for HIV post-exposure

Objectives: To assess HIV-1 post-exposure prophylaxis (PEP) non-completion at day 28, comparing ritonavir-boosted lopinavir versus cobicistat-boosted elvitegravir as a single-tablet regimen (STR), using tenofovir disoproxil fumarate/emtricitabine with both of these therapies. Methods: A prospective, open, randomized clinical trial was performed. Individuals attending the emergency room due to potential sexual exposure to HIV and who met criteria for PEP were randomized 1:3 into two groups receiving either 400/100mg of lopinavir/ritonavir (n=38) or 150/150mg of elvitegravir/cobicistat (n=119), with both groups also receiving 245/200mg of tenofovir disoproxil fumarate/emtricitabine. Five follow-up visits were scheduled at days 1, 10, 28, 90 and 180. The primary endpoint was PEP non-completion at day 28. Secondary endpoints were adherence, adverse effects and rate of seroconversions. Clinical trials. gov number: NCT08431173. Results: Median age was 32 years and 95% were males. PEP non-completion at day 28 was 36% (n=57), with a trend to be higher in the lopinavir/ritonavir arm [lopinavir/ritonavir 47% (n=18) versus elvitegravir/cobicistat 33% (n=39), P=0.10]. We performed a modified ITT analysis including only those patients who attended on day 1. PEP non-completion in this subgroup was higher in the lopinavir/ritonavir arm than in the elvitegravir/cobicistat arm (33% versus 15%, respectively, P=0.04). Poor adherence was significantly higher in the lopinavir/ritonavir arm versus the elvitegravir/cobicistat arm (47% versus 9%, respectively, P<0.0001). Adverse events were reported by 73 patients (59%), and were significantly morecommon in the lopinavir/ritonavir arm (90% versus 49%, P=0.0001). A seroconversion was observed in the elvitegravir/cobicistat arm in a patient with multiple exposures before and after PEP. Conclusions: A higher PEP non-completion, poor adherence and adverse eventswere observed in patients allocated to the lopinavir/ritonavir arm, suggesting that STR elvitegravir/cobicistat is awell-tolerated antiretroviral for PEP.