Heavily treatment-experienced people living with HIV in the OPERA® cohort: population characteristics and clinical outcomes.

BACKGROUND: Multi-class resistance, intolerance, and drug-drug interactions can result in unique antiretroviral (ART) combinations for heavily treatment-experienced (HTE) people living with HIV (PLWH). We aimed to compare clinical outcomes between HTE and non-HTE PLWH. METHODS: Eligible ART-experienced PLWH in care in the OPERA® Cohort were identified in a cross-sectional manner on December 31, 2016 and observed from the date of initiation of the ART regimen taken on December 31, 2016 until loss to follow up, death, study end (December 31, 2018), or becoming HTE (non-HTE group only). In the absence of resistance data, HTE was defined based on the ART regimens used (i.e., exposed to ≥ 3 core agent classes or regimen suggestive of HTE). Time to virologic undetectability, failure, and immunologic preservation were assessed using Kaplan-Meier methods; cumulative probabilities were compared between the two groups. Regimen changes, incident morbidities, and death were described. RESULTS: A total of 24,183 PLWH (2277 HTE PLWH, 21,906 non-HTE) were followed for a median of 28 months (IQR 21, 38). Viremic HTE PLWH (viral load [VL] ≥ 50 copies/mL) were less likely to achieve undetectability (VL < 50 copies/mL; 24-month cumulative probability: 80% [95% Confidence Interval 77-82]) than their non-HTE counterparts (85% [84-86]). No difference was observed in the probability of maintaining VLs < 200 copies/mL over the first 48 months after achieving suppression (< 50 copies/mL). HTE PLWH were less likely than non-HTE PLWH to maintain CD4 cell counts ≥ 200 cells/µL (24-month cumulative probability: 95% HTE [91-93]; 97% non-HTE [97-97]), and more likely to change regimens (45% HTE; 41% non-HTE). Incident non-AIDS defining event (ADE) morbidities were common in both populations, though more likely among HTE PLWH (45%) than non-HTE PLWH (35%). Incident ADE morbidities and deaths were uncommon among HTE (ADEs 5%; deaths 2%) and non-HTE (ADEs 2%; deaths 1%) PLWH. CONCLUSIONS: HTE PLWH were at greater risk of unfavorable treatment outcomes than non-HTE PLWH, suggesting additional therapeutic options are needed for this vulnerable population.

Virologic Outcomes Among People Living With Human Immunodeficiency Virus With High Pretherapy Viral Load Burden Initiating on Common Core Agents.

BACKGROUND: People living with human immunodeficiency virus (PLWH) initiating antiretroviral therapy (ART) with viral loads (VLs) ≥100 000 copies/mL are less likely to achieve virologic success, but few studies have characterized real-world treatment outcomes. METHODS: ART-naive PLWH with VLs ≥100 000 copies/mL initiating dolutegravir (DTG), elvitegravir (EVG), raltegravir (RAL), or darunavir (DRV) between 12 August 2013 and 31 July 2017 were identified from the OPERA database. Virologic failure was defined as (i) 2 consecutive VLs ≥200 copies/mL after 36 weeks of ART; (ii) 1 VL ≥200 copies/mL with core agent discontinuation after 36 weeks; (iii) 2 consecutive VLs ≥200 copies/mL after suppression (≤50 copies/mL) before 36 weeks; or (iv) 1 VL ≥200 copies/mL with discontinuation after suppression before 36 weeks. Cox modeling estimated the association between regimen and virologic failure. RESULTS: There were 2038 ART-naive patients with high VL who initiated DTG (36%), EVG (46%), DRV (16%), or RAL (2%). Median follow-up was 18.1 (interquartile range, 12.4-28.9) months. EVG and DTG initiators were similar at baseline, but RAL initiators were older and more likely to be female with low CD4 cell counts while DRV initiators differed notably on factors associated with treatment failure. Virologic failure was experienced by 9.2% DTG, 13.2% EVG, 18.4% RAL, and 18.8% DRV initiators. Compared to DTG, the adjusted hazard ratio (95% confidence interval) was 1.46 (1.05-2.03) for EVG, 2.24 (1.50-3.34) for DRV, and 4.13 (1.85-9.24) for RAL. CONCLUSIONS: ART-naive PLWH with high VLs initiating on DTG were significantly less likely to experience virologic failure compared to EVG, RAL, and DRV initiators.Antiretroviral therapy-naïve people living with HIV (PLWH) initiating therapy with viral loads ≥100,000 copies/mL varied markedly at baseline. In adjusted models, PLWH initiating dolutegravir-based regimens were less likely to experience virologic failure as compared to elvitegravir, raltegravir and darunavir initiators.

Virologic Outcomes Among ART-Naïve Individuals Initiating Dolutegravir, Elvitegravir, Raltegravir or Darunavir: An Observational Study.

INTRODUCTION: Dolutegravir (DTG), Elvitegravir (EVG), Raltegravir (RAL) and Darunavir (DRV) are commonly prescribed core agents for antiretroviral therapy (ART), and a need exists to compare their clinical effectiveness, as defined by virologic failure risks in real-world settings. METHODS: This observational analysis of a US clinical cohort consisted of ART-naïve people living with HIV (PLWH) in the OPERA database initiating DTG-, EVG-, RAL- or DRV-based regimens between August 2013 and July 2016, with follow-up to July 2017. PLWH were observed from first core agent initiation until core agent discontinuation, clinical activity cessation, death, or study end. Key outcomes included viral suppression (HIV RNA < 50 copies/mL) and confirmed virologic failure (two consecutive viral loads > 200 copies/mL or a viral load > 200 copies/mL followed by discontinuation). Association between core agent and time to virologic failure was assessed with multivariate Cox proportional hazards models. RESULTS: Overall, 4049 ART-naïve PLWH initiated EVG (47.4%), DTG (34.7%), DRV (14.6%), or RAL (3.2%). DTG and EVG initiators had generally similar baseline demographics and clinical characteristics, including race, risk of infection, baseline viral load, and baseline CD4 levels. RAL and DRV initiators were older and generally sicker than DTG initiators. During follow-up, more DTG initiators achieved virologic suppression (78.7%) compared with EVG (73.6%; p < 0.05), RAL (51.9%; p < 0.0001) and DRV (48.6%; p < 0.0001) initiators. Compared to DTG, both RAL and DRV were associated with higher rates of virologic failure, with adjusted hazard ratios (95% confidence interval) of 4.70 (3.03, 7.30) and 2.38 (1.72, 3.29), respectively. No difference was observed between EVG and DTG with an adjusted hazard ratio of 1.24 (0.94, 1.64). CONCLUSION: In this large cohort representative of PLWH in care in the US, ART-naïve PLWH prescribed DTG had better virologic outcomes than RAL and DRV, but had virologic failure risks comparable to EVG, although RAL and DRV were preferentially prescribed to sicker individuals. FUNDING: ViiV Healthcare.