Treatment Outcomes of Integrase Inhibitors, Boosted Protease Inhibitors and Nonnucleoside Reverse Transcriptase Inhibitors in Antiretroviral-Naïve Persons Starting Treatment

A Mocroft; B Neesgard; R Zangerle; A Rieger; A Castagna; V Spagnuolo; A Antinori; FC Lampe; M Youle; JJ Vehreschild; C Mussini; V Borghi; J Begovac; C Duvivier; HF Gunthard; A Rauch; J Tiraboschi; N Chkhartishvili; N Bolokadze; F Wit; JC Wasmuth; S De Wit; C Necsoi; C Pradier; V Svedhem; C Stephan; K Petoumenos; H Garges; F Rogatto; L Peters; L Ryom

Disclosures

HIV Medicine. 2020;21(9):599-606. 

In This Article

Abstract and Introduction

Abstract

Objectives: Although outcomes of antiretroviral therapy (ART) have been evaluated in randomized controlled trials, experiences from subpopulations defined by age, CD4 count or viral load (VL) in heterogeneous real-world settings are limited.

Methods: The study design was an international multicohort collaboration. Logistic regression was used to compare virological and immunological outcomes at 12 ± 3 months after starting ART with an integrase strand transfer inhibitor (INSTI), contemporary nonnucleoside reverse transcriptase inhibitor (NNRTI) or boosted protease inhibitor (PI/b) with two nucleos(t)ides after 1 January 2012. The composite treatment outcome (cTO) defined success as VL < 200 HIV-1 RNA copies/mL with no regimen change and no AIDS/death events. Immunological success was defined as a CD4 count > 750 cells/μL or a 33% increase where the baseline CD4 count was ≥ 500 cells/μL. Poisson regression compared clinical failures (AIDS/death ≥ 14 days after starting ART). Interactions between ART class and age, CD4 count, and VL were determined for each endpoint.

Results: Of 5198 ART-naïve persons in the International Cohort Consortium of Infectious Diseases (RESPOND), 45.4% started INSTIs, 26.0% PI/b and 28.7% NNRTIs; 880 (17.4%) were aged > 50 years, 2539 (49.4%) had CD4 counts < 350 cells/μL and 1891 (36.8%) had VL > 100 000 copies/mL. Differences in virological and immunological success and clinical failure among ART classes were similar across age groups (≤ 40, 40–50 and > 50 years), CD4 count categories (≤ 350 vs. > 350 cells/μL) and VL categories at ART initiation (≤ 100 000 vs. > 100 000 copies/mL), with all investigated interactions being nonsignificant (P > 0.05).

Conclusions: Differences among ART classes in virological, immunological and clinical outcomes in ART-naïve participants were consistent irrespective of age, immune suppression or VL at ART initiation. While confounding by indication cannot be excluded, this provides reassuring evidence that such subpopulations will equally benefit from contemporary ART.

Introduction

Randomized clinical trials of antiretroviral therapy (ART)-naïve persons suggest either similar or superior immunological and virological responses with integrase strand transfer inhibitor (INSTI)-containing regimens compared to contemporary boosted protease inhibitors (PI/bs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs).[1–7] There are no adequately powered studies assessing longer term clinical outcomes with INSTIs. Most randomized clinical trials report results within relevant subgroups, such as viral load (VL), CD4 count and age subgroups. In general, such trials report no differences across these relevant subgroups,[2] or small and sometimes nonsignificant differences favouring INSTI-containing regimens in older persons,[6] those with higher baseline CD4 counts[4,6] or those with higher baseline VLs.[1,4,8] Smaller differences were reported between an INSTI (dolutegravir) and an NNRTI (efavirenz) in those with high VL or low CD4 count or aged > 50 years at baseline.[7] In contrast, cohort studies lack randomization, but they may represent a more real-world setting for investigating the response to different ART classes and are often better powered for subgroup comparisons. Previous cohort studies, including an analysis from the International Cohort Consortium of Infectious Diseases (RESPOND), have shown a more favourable virological and/or immunological response in those starting INSTIs compared to other ART classes,[9–11] but it is not clear if this finding is consistent across key subpopulations.

The aim of this study was to compare shorter term virological and immunological outcomes and clinical events of AIDS/death in ART-naïve persons starting ART in RESPOND with either an INSTI, PI/b or NNRTI regimen in key subgroups.

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