INSTI-Based Triple Regimens in Treatment-Naïve HIV-Infected Patients Are Associated With HIV-RNA Viral Load Suppression at Ultralow Levels

Sidonie Lambert-Niclot; Anders Boyd; Djeneba Fofana; Nadia Valin; Marc Wirden; Jean-Luc Meynard; Romain Palich; Rachid Agher; Marc-Antoine Valantin; Vincent Calvez; Christine Katlama; Pierre-Marie Girard; Anne-Geneviève Marcelin; Laurence Morand-Joubert

doi:10.1093/ofid/ofz177

INSTI-Based Triple Regimens in Treatment-Naïve HIV-Infected Patients Are Associated With HIV-RNA Viral Load Suppression at Ultralow Levels

Open Forum Infect Dis. 2019 Apr 10;6(5):ofz177. doi: 10.1093/ofid/ofz177. eCollection 2019 May.

Authors

Sidonie Lambert-Niclot^{1

2

3}, Anders Boyd², Djeneba Fofana^{2

3}, Nadia Valin⁴, Marc Wirden^{2

5}, Jean-Luc Meynard⁴, Romain Palich^{1

2

6}, Rachid Agher⁶, Marc-Antoine Valantin^{1

2

6}, Vincent Calvez^{1

2

5}, Christine Katlama^{1

2

6}, Pierre-Marie Girard^{1

2

4}, Anne-Geneviève Marcelin^{1

2

5}, Laurence Morand-Joubert^{1

2

3}

Affiliations

¹ Sorbonne Université, Paris, France.
² INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Paris, France.
³ AP-HP, Hôpital Saint-Antoine, Laboratoire de Virologie, Paris, France.
⁴ AP-HP, Hôpital Saint-Antoine, Département de Maladies Infectieuses, Paris, France.
⁵ AP-HP, Hôpital Pitié Salpêtrière, Laboratoire de Virologie, Paris, France.
⁶ AP-HP, Hôpital Pitié Salpêtrière, Département de Maladies Infectieuses, Paris, France.

Abstract

Background: During antiretroviral therapy (ART), HIV-1-infected patients may present with ultralow (UL) HIV-RNA viral loads (VLs) below quantification levels of current assays. Reasons for UL-VL detection and its relation to virological rebound (VR) are unclear.

Methods: HIV-1-infected, ART-naïve patients followed at 2 university hospitals were included. All participants had an HIV-RNA >200 copies/mL at ART initiation and achieved a VL <50 copies/mL during ART. UL-VL was determined by the presence/absence of polymerase chain reaction signal detected using a commercially available assay (COBAS, TaqMan, Roche). Random-effects Poisson regression was used for assessing determinants of UL-VL not detected overtime and conditional risk set analysis for VR (1 VL > 200 copies/mL or 2 VL > 50 copies/mL) while accounting for frequency of VL measurements.

Results: Between 2009 and 2013, 717 patients initiated ART containing 2 nucleos(-t)ide reverse transcriptase inhibitors (NRTIs) plus a non-NRTI (29.4%), a protease inhibitor (58.4%), or an integrase-strand transfer inhibitor (INSTI; 12.1%). During a median (interquartile range) 3.4 (2.3-4.6) years, 676 (94.3%) patients achieved UL-VL not detected. In multivariable analysis, UL-VL not detected overtime was associated with younger age (P < .001), female gender (P = .04), lower baseline VL (P < .001), baseline CD4+ >500 vs <350/mm³ (P < .001), and INSTI-containing ART (P = .009). One hundred thirty-one (18.3%) patients had VR during follow-up, which was independently associated with a CD4/CD8 ratio <0.8 during follow-up (P = .01) and time spent with UL-VL not detected (P < .001). When UL-VL not detected occurred for ≥50% of the follow-up duration (n = 290), faster time to reach UL-VL not detected (P < .001), faster CD4+ T-cell count increase (P = .03), and faster CD4/CD8 ratio increase (P = .001) were observed.

Conclusions: VL suppression at an ultralow level is associated with INSTI-class ART initiation. Extensive VL suppression below ultralow detection could improve immune reconstitution.

Keywords: HIV; initiation antiretroviral therapy; integrase inhibitor; residual viremia.