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

Discussion

This analysis of ART-naïve persons starting contemporary ART in the large RESPOND cohort collaboration focused on a composite treatment outcome and immunological success at 12 months and new AIDS diagnosis or death occurring more than 14 days after starting ART. While there were some differences in cTO and immunological success in favour of INSTIs, findings were consistent across subgroups defined by age, CD4 count, VL and severe immune suppression (AIDS or CD4 count ≤ 200 cells/μL).

We found some evidence that virological treatment response to INSTIs was better than that to contemporary PI/bs using both composite outcomes and an on-treatment analysis, consistent with recent meta-analyses,[15,16] open-label studies[17] and findings from observational studies.[9,11,18] We also found a slightly better immunological response with INSTIs compared to NNRTIs, as has been previously shown.[6,7,19] Importantly, the differences in immunological and virological responses found when comparing the three antiretroviral classes were consistent in the key subgroups investigated. While we adjusted for important confounders, such as age and nadir CD4 count, we cannot exclude confounding by indication. We chose a relatively high CD4 count for immunological response, reflecting the comparatively high CD4 count nadir in the included individuals, as well as evidence that the incidence of AIDS no longer decreases at CD4 counts > 750 cells/μL,[14] but found consistent results in sensitivity analyses using lower CD4 count increases to define immunological response.

To our knowledge, we are the first to show no differences in AIDS or mortality outcomes comparing INSTIs, PI/bs and NNRTIs, albeit with limited power. We focused on events occurring > 14 days after ART to reduce the impact of early events caused by late presentation. The median time to event remained short, suggesting that some of the events were caused by uncontrolled HIV infection and/or late presentation. We focused on AIDS and death to reduce confounding by indication related to the choice of initial ART in persons with underlying comorbidities. Of note, our findings were similar across key subgroups, less often considered particularly in cohort studies. This finding is of direct clinical relevance and can be used in routine clinic settings to reassure persons starting ART.

The main limitation of our study is that we cannot rule out confounding by indication. We were not powered to look at individual antiretrovirals and it is possible that results differ within ART classes for specific agents. The major strengths of this study were the inclusion of routine clinic populations, inclusion of clinical events as an endpoint, and the focus on whether results were consistent across key subgroups.

To conclude, 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 modern ART.

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