Antiretroviral Treatment Outcomes Among Late HIV Presenters Initiating Treatment With Integrase Inhibitors or Protease Inhibitors

G Schuettfort; L Boekenkamp; A Cabello; AG Cotter; P De Leuw; J Doctor; M Górgolas; L Hamzah; E Herrmann; G Kann; P Khaykin; PW Mallon; A Mena; M Del Palacio Tamarit; CA Sabin; C Stephan; T Wolf; AE Haberl


HIV Medicine. 2021;22(1):47-53. 

In This Article

Abstract and Introduction


Objectives: The aim of the study was to investigate the efficacy and safety of first-line antiretroviral therapy (ART) with integrase inhibitor (INI) or protease inhibitor (PI)-based regimens in patients with low CD4 cell counts and/or an AIDS-defining disease.

Methods: We conducted a retrospective, multicentre analysis to investigate discontinuation proportions and virological response in patients with CD4 cell counts < 200 cells/μL and/or AIDS-defining disease when starting first-line ART. Proportions of those discontinuing ART were compared using univariate analysis. Virological response was analysed using the Food & Drug Administration (FDA) snapshot analysis (HIV-1 RNA < 50 HIV-1 RNA copies/mL at week 48).

Results: Two hundred and eighteen late presenters were included in the study: 13.8% were women and 23.8% were of non-European ethnicity, and the mean baseline CD4 count was 91 cells/μL (standard deviation 112 cells/μL). A total of 131 late presenters started on INI- and 87 on PI-based treatment. It was found that 86.1% of patients treated with INIs and 81.1% of patients treated with PIs had a viral load < 50 copies/mL at week 48; proportions of discontinuation because of adverse events were 6.1% in the INI group and 11.5% in the PI group. No significant differences in discontinuation proportions were observed at week 12 or 48 between INI- and PI-based regimens (P = 0.76 and 0.52, respectively). Virological response was equally good in those receiving INIs and those receiving PIs (86.1% vs. 81.1%, respectively; P = 0.36).

Conclusions: In a European cohort of late presenters starting first-line INI or PI-based ART regimens, there were no significant differences in discontinuation proportions or virological response at week 48.


Individuals with advanced HIV infection – a low CD4 cell count and/or an AIDS-defining condition – at the time of HIV diagnosis (hereafter referred to as "late presenters")[1] have been demonstrated to have poorer health outcomes compared to those diagnosed with a CD4 cell count > 350 cells/μL.[2] The number of late HIV presenters remains high across Europe.[3] Prompt initiation of antiretroviral treatment (ART) in those with advanced HIV infection is recommended;[4] however, the optimal initial ART regimen for these individuals has not yet been established.[5] Protease inhibitor (PI)-containing regimens are frequently used in individuals with advanced HIV infection,[6] but there are few data on the outcomes of integrase inhibitor (INI)-based regimens in this population.[7–9]

INIs are promising candidates for treatment combinations in those with advanced HIV infection, and in particular late presenters, as a consequence of their antiviral activity and their ability to produce a rapid decline in viral load, with potentially fewer side effects and different metabolism pathways compared to other types of regimen.[10] Data suggest that starting INI-based regimens in ART-naïve individuals with a CD4 cell count > 500 cells/μL is safe and effective[11,12] as is switching from a PI-based regimen to an INI-based one in individuals who are already virologically suppressed.[13,14] In patients with a CD4 count ≥ 200 and < 500, there are still limited data available, but the use of INI-based regimens also seems to be safe in these patients.[15] However, there is a paucity of data on which type of regimen performs best in those with advanced HIV disease in terms of viral efficacy, immune reconstitution, and improvement of AIDS-defining conditions/opportunistic infections (OIs) and adverse events.

The presence of active OIs is often an exclusion criterion in randomized clinical trials (RCTs), as individuals with these infections usually experience additional comorbidities and are at increased risk of drug–drug interactions (DDIs) and treatment failure. As a consequence, late presenters are not well represented in RCTs comparing the efficacies of different regimens. Strategic trials in this population thus far have focused on the optimal time of treatment initiation to prevent immune reconstitution syndromes (IRIS)[16] or to improve the disease course of already diagnosed OIs.[4] Outside of these trials, no specific combinations have been compared either in retrospective analysis or in sufficiently powered RCTs. As a result, all regimens listed in international treatment guidelines are considered to be equally suitable options for first-line treatment for this population.[17,18] Thus, the choice of ART regimen in late presenters remains the individual decision of the HIV health care provider.


This study aimed to investigate the efficacy and safety of first-line ART with either an INI- or a PI-based regimen in individuals diagnosed with HIV infection with advanced disease.