Author: Margolis, David M ; Hicks, Charles B ; Eron, Joseph J ; Kuruc, Joann D ; Gay, Cynthia L ; Filiatreau, Lindsey M ; McKellar, Mehri S ; Keys, Jessica R ; Ferrari, Guido ; McGee, Kara S

AbstractBackgroundAntiretroviral therapy (ART) is recommended for all individuals with HIV infection, including those with acute HIV-1 infection (AHI). While recommendations are similar to those for chronic infection, efficacy data regarding treatment of acute HIV is limited.MethodsThis was a single arm, 96-week study of a once-daily integrase inhibitor (INSTI)-based regimen using elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF) in AHI. Primary endpoint was proportion of participants with HIV-1 RNA <200 copies/mL and <50 copies/mL by treatment weeks 24 and 48, respectively. We also examined time to viral suppression and weight gain after treatment initiation. Outcomes and characteristics were compared with a historical AHI cohort using a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen with efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF).ResultsThirty-three participants with AHI were enrolled with 31 available for analyses. Most were African American (61%) and men who have sex with men (73%). Median age was 26 (IQR 22–42). Demographics were similar between the two AHI cohorts. By Week 24, 100% in the INSTI and 99% in the NNRTI cohort were <200 copies/mL; by Week 48, 100% in both cohorts were <50 copies/mL. Time to viral suppression was shorter in the INSTI cohort (median 54 versus 99 days). Mean weight change was similar with a 3.6 kg increase in the INSTI cohort and 2.4 kg in the NNRTI cohort at 96 weeks.ConclusionsINSTI-based ART during AHI resulted in rapid and sustained viral suppression. Over 96 weeks, weight increased in the INSTI-based cohort but was similar to weight increase in a historical NNRTI-based AHI cohort.

03 Jan 2025·Journal of Antimicrobial Chemotherapy

No accelerated progression of subclinical atherosclerosis with integrase strand transfer inhibitors compared to non-nucleoside reverse transcriptase inhibitors

Article

Author: Fernández-González, Marta ; Botella, Ángela ; García-Abellán, Javier ; Padilla, Sergio ; Mascarell, Paula ; Agulló, Vanesa ; García, José A ; Gutiérrez, Félix ; Masiá, Mar

AbstractBackgroundThe role of integrase strand transfer inhibitors (INSTI) in the cardiovascular risk of people with HIV is controversial.ObjectivesTo assess the association of INSTI to subclinical atherosclerosis progression measured with the carotid intima-media thickness (cIMT).MethodsProspective study in virologically suppressed people with HIV receiving INSTI- or NNRTI-based regimens. cIMT was measured at baseline, 48 and 96 weeks. cIMT progression was analysed both as a continuous and categorical variable, defined as cIMT increase ≥ 10% and/or new carotid plaque. Adjustments through Cox proportional hazard regression and linear mixed models, and propensity score matching were conducted.Results190 participants were recruited and 173 completed the 96 week follow-up. 107 (56.3%) were receiving an INSTI-containing, 128 (67.4%) a NNRTI-containing and 45 (23.7%) a NNRTI plus an INSTI-containing regimen. The overall median (IQR) 2-year change of cIMT was 0.029 (−0.041 to 0.124) mm; 87 (45.8%) participants experienced a cIMT increase ≥ 10%, of whom 54 (28.4%) developed a new carotid plaque. Adjusted Cox regression showed no differences between INSTI and NNRTI groups in the categorical 2-year progression of cIMT, both including or excluding participants receiving INSTI + NNRTI. Similar results were observed for the continuous cIMT increase through adjusted linear mixed models. Propensity score matching showed no significant differences in the 2 year cIMT change between treatment groups [0.049 mm (−0.031–0.103) in the INSTI group versus 0.047 mm (−0.023–0.115) in the NNRTI group; P = 0.647]. cIMT progression was associated with traditional cardiovascular risk factors.ConclusionsINSTI-based regimens are not associated with increased progression of subclinical atherosclerosis when compared to NNRTI.

01 Jan 2025·AIDS Research and Human Retroviruses

A Randomized, Double-Blind, Placebo-Controlled, Short-Term Monotherapy Study of MK-6186, an HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitor, in Treatment-Naïve HIV-Infected Participants

Article

Author: De Lepeleire, Inge ; Stegemann, Miriam S. ; Cilissen, Caroline ; Schürmann, Dirk ; Pfäfflin, Frieder ; Larson, Patrick J. ; Anderson, Matt S. ; Stoch, Selwyn A. ; Hüser, Andreas ; Rizk, Matthew L. ; Wagner, Frank ; Hofmann, Jörg ; Iwamoto, Marian ; Däumer, Martin

Objective: To assess the antiviral activity, pharmacokinetics, and safety of MK-6186 in HIV-1 non-nucleoside reverse transcriptase inhibitor (NNRTI)-naïve, HIV-1-infected male participants. Design: Double-blind, randomized, two-panel study. Methods: In 2 sequential panels, 18 participants received MK-6186 (40 mg [Panel A] or 150 mg [Panel B]) or matching placebo once daily for 7 days. Plasma samples were collected for measurement of HIV-1 RNA levels and MK-6186 pharmacokinetics. Results: For the mean change from baseline in HIV-1 RNA (log₁₀ copies/mL) at 24 h post Day 7 dose, the mean difference (90% confidence interval) between MK-6186 and placebo was -1.54 (-1.73, -1.34) in the 40-mg group and -1.28 (-1.81, -0.75) in the 150-mg group. One participant in the 150-mg group had viral rebound at 24 h after Day 6 dosing (Day 7 predose) associated with outgrowth of the V106A minority variant. Ultra-deep sequencing confirmed expansion of this predose minority variant from 0.26% to 63.67%. No outgrowth or rebound was seen in another participant in whom a V106A minority variant was also detected. MK-6186 was generally well tolerated. MK-6186 was rapidly absorbed with peak concentrations at 2 h followed by a biphasic decline. The effective t½ of MK-6186 was 43.9 to 48.7 h. Steady state was not achieved. Conclusions: Daily monotherapy with MK-6186 demonstrated robust antiviral activity with maximal antiviral activity at a dose of 40 mg. One participant in the 150-mg group exhibited viral rebound with outgrowth of the resistant V106A minority variant, demonstrating a risk of resistance development typical of NNRTIs. The reason for this outgrowth remains unclear as no outgrowth occurred in a participant in the 40-mg group in whom the V106A minority variant was also detected. MK-6186 may be an alternative next-generation NNRTI in combination therapy, in that combination antiretroviral therapy could prevent outgrowth of resistant minority variants.

100 Deals associated with NNRTI (AiCuris)

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Indication	Highest Phase	Country/Location	Organization	Date
HIV Infections	Phase 1	DE	Aicuris Anti-Infective Cures AG	-

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


IAS2013	Not Applicable	HIV Infections	994	3-drug NVP-based	-	-	01 Jan 2013
				3-drug EFV-based
IAS2012	Not Applicable	Malaria \| HIV Infections	340	LPV/r-based ART	ennhtxwjqx(hpjwxudlom) = vfvqyhtnjh htjuxnrzwk (ficfdflcuu )	-	01 Jan 2012
				NNRTI-based ART	ennhtxwjqx(hpjwxudlom) = jirvrpmzkq htjuxnrzwk (ficfdflcuu )
IAS2010	Not Applicable	HIV Infections	64	PI-based combinations	wtxwlosywp(uxadsthhkm) = spnvanascp fszjdjaenb (zbimpmdqug ) View more	-	01 Jan 2010
				NNRTI-based combinations	wtxwlosywp(uxadsthhkm) = wyfwtfjzqr fszjdjaenb (zbimpmdqug ) View more
TASTE study (IAS2008)	Not Applicable	-	244	AZT/D4T+3TC+NNRTI/PI	irpdkiibsi(aivowklrda) = 6 cases in the switch group fmaedyddwp (atzrojdelm ) View more	-	01 Jan 2008
				ABC+3TC+NNRTI/PI
IAS2007	Not Applicable	Cerebrospinal Fluid Leak	17	Tenofovir/emtricitabine + 1 NNRTI	sfgnizaojo(fccjjmssfb) = zbedswclar vdrkzhagsn (mqnhpebhda ) View more	-	01 Jan 2007
IAS2007	Not Applicable	-	185	AZT/D4T+3TC+NNRTI/PI	nebjrjzapx(vbjheumzxe) = fnzqoeeqwl mvidjwldea (rqycorkuok ) View more	-	01 Jan 2007
				ABC+3TC+NNRTI/PI	nebjrjzapx(vbjheumzxe) = lhzxiclkge mvidjwldea (rqycorkuok ) View more

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