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

Methods

Study Design and Participants

The International Cohort Consortium of Infectious Diseases (RESPOND) is a collaboration of 17 cohort studies, including 29 432 HIV-1-positive persons from across Europe and Australia.[12] Standardized data including information on demographics, HIV-related factors, ART, coinfections, comorbidities and various biomarkers are collected at enrolment and updated annually (details at https://www.chip.dk/Studies/RESPOND). All cohorts used the HIV Cohorts Data Exchange Protocol (HICDEP) for data collection (details at https://hicdep.org/) and deaths are centrally validated using the Coding of Death in HIV (CoDe) methodology.[13]

Persons aged > 18 years were included in this analysis if they were ART-naïve with a VL > 200 HIV-1 RNA copies/mL and started exactly three antiretrovirals during prospective follow-up after 1 January 2012 with either an INSTI (dolutegravir, elvitegravir, raltegravir or bictegravir), PI/b (darunavir or atazanavir) or NNRTI (efavirenz or rilpivirine) and had a CD4 count and VL measured in the 12 months prior to starting ART (for those without baseline data, the first CD4 count or VL after starting ART was used, at most 12 weeks after ART initiation).

Outcomes

Baseline was defined as the date of starting ART. Persons were stratified a priori according to baseline VL (≤ 100 000 or > 100 000 copies/mL), baseline CD4 count (≤ 350 or > 350 cells/μL), age (≤ 40, 41–50 or > 50 years) and presence of severe immunosuppression (CD4 count ≤ 200 cells/μL or clinical AIDS).

Immunological success was defined as a CD4 count > 750 cells/μL (where the baseline CD4 count was < 500 cells/μL) or a 33% increase in CD4 count (where the baseline CD4 count was ≥ 500 cells/μL), reflecting the finding that the incidence of AIDS/death is no longer increased at CD4 counts > 750 cells/μL.[14] The composite treatment outcome (cTO) defined success as VL < 200 copies/mL with no regimen change and no AIDS/death events. Switches in coformulation or change of booster were not considered to be a regimen change, while switches to a two-drug regimen or of an individual component, such as tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF), were considered to be changes as they may be related to drug toxicity.

A VL < 200 copies/mL was used following consensus agreement within the RESPOND virological outcomes working group reflecting cohort differences in lower limits of detection. A window of 3 months was used; immunological and cTO success was assessed at 12 ± 3 months. Clinical outcome was defined as the first new AIDS diagnosis or death from any cause occurring > 14 days after baseline.

Statistical Methods

Logistic regression was used to assess the odds of cTO and immunological success, testing the interaction between ART class and baseline VL, CD4 count, presence of severe immunosuppression and age. Further analyses used VL < 50 copies/mL to define cTO success, and an on-treatment analysis considered only VL < 200 copies/mL (or 50 copies/mL) among those with data who remained on their initial regimen (on-treatment virological success). Poisson regression was used to investigate AIDS/death, testing the interaction between treatment class and baseline VL, CD4 count, presence of severe immune suppression and age. Analyses were adjusted for demographic (race, HIV exposure group, gender, ethnic origin, viral hepatitis B and C status, year of starting ART, cohort and age group), clinical (duration of HIV infection and nucleoside backbone) and laboratory (CD4 count and VL) parameters, all measured at baseline.

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