Research Article: Virological failure and all-cause mortality in HIV-positive adults with low-level viremia during antiretroviral treatment

Date Published: July 6, 2017

Publisher: Public Library of Science

Author(s): Olof Elvstam, Patrik Medstrand, Aylin Yilmaz, Per-Erik Isberg, Magnus Gisslén, Per Björkman, Nicolas Sluis-Cremer.

http://doi.org/10.1371/journal.pone.0180761

Abstract

Although most HIV-infected individuals achieve undetectable viremia during antiretroviral therapy (ART), a subset have low-level viremia (LLV) of varying duration and magnitude. The impact of LLV on treatment outcomes is unclear. We investigated the association between LLV and virological failure and/or all-cause mortality among Swedish patients receiving ART.

HIV-infected patients from two Swedish HIV centers were identified from the nationwide register InfCare HIV. Subjects aged ≥15 years with triple agent ART were included at 12 months after treatment initiation if ≥2 following viral load measurements were available. Patients with 2 consecutive HIV RNA values ≥1000 copies/mL at this time point were excluded. Participants were stratified into four categories depending on viremia profiles: permanently suppressed viremia (<50 copies/mL), LLV 50–199 copies/mL, LLV 200–999 copies/mL and viremia ≥1000 copies/mL. Association between all four viremia categories and all-cause death was calculated using survival analysis with viremia as a time-varying covariate, so that patients could change viremia category during follow-up. Association between the three lower categories and virological failure (≥2 consecutive measurements ≥1000 copies/mL) was calculated in a similar manner. LLV 50–199 copies/mL was recorded in 70/1015 patients (6.9%) and LLV 200–999 copies/mL in 89 (8.8%) during 7812 person-years of follow-up (median 6.5 years). LLV 200–999 copies/mL was associated with virological failure (adjusted hazard ratio 3.14 [95% confidence interval 1.41–7.03, p<0.01]), whereas LLV 50–199 copies/mL was not (1.01 [0.34–4.31, p = 0.99]; median follow-up 4.5 years). LLV 200–999 copies/mL had an adjusted mortality hazard ratio of 2.29 (0.98–5.32, p = 0.05) and LLV 50–199 copies/mL of 2.19 (0.90–5.37, p = 0.09). In this Swedish cohort followed during ART for a median of 4.5 years, LLV 200–999 copies/mL was independently associated with virological failure. Patients with LLV had higher rates of all-cause mortality, although not statistically significant in multivariate analysis.

Partial Text

Although antiretroviral treatment (ART) improves survival and health in people living with HIV (PLHIV), mortality among PLHIV remains elevated compared to that in matched population controls [1, 2]. The reasons for this are not completely understood. In most persons receiving ART, HIV RNA cannot be detected in plasma using current routine methods with a lower limit of detection <50 copies/mL [3]. Detection of HIV RNA in plasma during ART may indicate emerging virological failure, which is variably defined as repeated HIV RNA values ≥50–1000 copies/mL [4–8], and usually with increasing viremia if treatment is not modified. A subset of patients, however, have low-level viremia (LLV), defined as repeated measurements between 20–150 copies/mL [8], 20–200 copies/ml [4], 50–200 copies/mL [5] or 50–1000 copies/mL [7]. In this cohort of Swedish PLHIV, LLV in the range 200–999 copies/mL during long-term ART was associated with increased risk of virological failure. For patients with LLV in a lower range (50–199 copies/mL) this risk was not significantly elevated. We also observed higher rates of all-cause mortality in individuals with LLV; however, this difference was not statistically significant in multivariate analysis. The proportion of patients with LLV in our population was similar to that previously reported from Europe and North America [19, 35]. Although LLV during ART is a well-recognized phenomenon, its impact on treatment outcomes is not clear. Moreover, the underlying mechanisms for LLV may be heterogeneous [9], and variable definitions of LLV exist. For these reasons, the optimal clinical management of patients with LLV is not obvious.   Source: http://doi.org/10.1371/journal.pone.0180761

 

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