Impact of Low-Level Viremia on Clinical and Virological Outcomes in Treated HIV Infected Patients

Marie Anne Vandehende, Suzanne Ingle, Margaret May, Matthias Cavassini, Amanda Mocroft, Peter Reiss, Jan Tate, Heidi M Crane, Jonathan Sterne, Genevieve Chene

Research output: Contribution to conferenceConference Poster

Abstract

Background: The goal of antiretroviral therapy (ART) is to maintain undetectable viremia but the impact, particularly on clinical outcomes, of low-level viremia (LLV) between 50 and 500 cp/ml remains unknown. Methodology: We analysed data from 19 cohorts in Europe and North America contributing to the ART Cohort Collaboration (ART-CC). Included patients started ART (“baseline”) with 2 NRTI and either a NNRTI or a PI (atazanavir, darunavir or lopinavir) boosted with ritonavir, and continued ART for at least 6 months, achieving viral load (VL) <50 cp/ml 3-9 months after initiating ART (“virological suppression”, VS). LLV50-199 was defined as at least 2 consecutive VL between 50 and 199 cp/ml and LLV200-499 as 2 consecutive VL between 50 and 499 cp/ml, with at least one between 200-499 cp/ml, after VS. All VL assays had 50 cp/ml lower limit of detection. We used Cox models stratified by cohort to estimate crude and adjusted hazard ratios (HR) for associations of LLV (50-199 cp/ml and 200-499 cp/ml, compared to <50cp/ml) with death, first AIDS event and first virological failure (VF, defined as 2 consecutive VL >=500 cp/ml or 1 VL >=500 cp/ml followed by modification of ART regimen). Adjustments were for baseline age, gender, ART regimen, transmission group, CD4 count, VL and AIDS, and period of ART initiation. LLV categories were considered as time-updated variables. Results: Among 17853 patients (mean age 40 years, male 76%, mean baseline CD4 238 cells/μL, NNRTI-based regimen 59%), 619 (3.5%) experienced at least one episode of LLV50-199 with no LLV200-499 (mean total duration: 6.8 months) and 481 (2.7%) at least one episode of LLV200-499 (mean total duration: 8.6 months). There were 478 deaths, 554 first post-ART AIDS events and 1022 VF in 68018 person-years follow-up. LLV200-499 was strongly associated with higher risk of VF (adjusted HR (aHR) 4.15, 95% CI 3.19-5.39). LLV50-199 was weakly associated with VF (aHR 1.40, 0.96-2.02). There was little evidence that LLV50-199 or LLV200-499 were associated with AIDS (aHR 1.13, 0.79-1.61 and 0.91, 0.61-1.28, respectively) or death (aHR 1.20, 0.79-1.83 and 1.12, 0.73-1.71 respectively), compared with prolonged suppression. Neither type of ART regimen (NNRTIversus PI/r-based) nor cumulative duration of LLV were associated with clinical or virological outcomes. Conclusions: Among patients virologically suppressed 3-9 months after starting ART, LLV200-499 was strongly associated with virological failure, but not with AIDS events or death. LLV50-199 had little impact on virological failure or clinical outcomes.
Original languageEnglish
Publication statusPublished - 3 Mar 2014
EventConference on Retroviruses and Opportunistic Infections - Boston, United States
Duration: 3 Mar 20146 Mar 2014

Conference

ConferenceConference on Retroviruses and Opportunistic Infections
CountryUnited States
CityBoston
Period3/03/146/03/14

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    Vandehende, M. A., Ingle, S., May, M., Cavassini, M., Mocroft, A., Reiss, P., Tate, J., Crane, H. M., Sterne, J., & Chene, G. (2014). Impact of Low-Level Viremia on Clinical and Virological Outcomes in Treated HIV Infected Patients. Poster session presented at Conference on Retroviruses and Opportunistic Infections, Boston, United States.